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CHAIRPERSON-
DRVENKATESH MULIMANI
SPEAKER-
DRVEERESH M
OSTEOSARCOMA
OSTEOSARCOMA
Osteosarcoma
 Malignant tumor characterized by production of
osteoid by malignant cells.
 composed of sarcomatous stroma...
• 2nd
m.c primary malignancy of the bone
• most common malignant tumor of bone in
children & young adult
• accounts for 20...
 all skeletal locations can be affected ; however,
most primary osteosarcomas occur at the sites of
the most rapid bone g...
most common sites
10 20 30 40 50 60 70 yrs
Osteogenic
Sarcoma
 may affect any age.
 Generally between 10- 25 yrs.
 primary high-grade osteosarcoma - second decade
of life.
 paroste...
ETIOLOGY
 Oncogenic viruses like Harvey and Moloney
mouse sarcoma virus(RNA virus) and polyoma
and SV 40 (DNA virus)
 Ra...
Clinical features
• Symptoms
1)Progressive pain-
results from microinfarctions .
2)night pain
only about 25% of patients e...
SIGNS
 fusiform swelling
 consistency : variegated
 dilated veins
 skin stretched and shiny
 local rise of temperatur...
GROSS APPEARANCE
 Situated in metaphysis of long bones (lower end
of femur,upper end of tibia and humerus)
 Appears as l...
Pathological Features
• ‘Mutton leg’
appearance
• Grayish white
• Edge stops at
epiphyseal
cartilage
Microsopy
• primarily osteoblastic,
fibroblastic, or
chondroblastic
• spindle cells
• malignant osteoid
producing cells
• ...
• intercellular matrix
scanty/ considerable amount
• myxomatous/cartilagenous/
osseous
• osteoclastic cell type – when
the...
TYPES
• PRIMARY OSTEOSARCOMA
 CONVENTIONAL OSTEOSARCOMA ( HIGH – GRADE)
 PERIOSTEAL OSTEOSARCOMA
 PAROSTEAL OSTEOSARCOM...
CONVENTIONAL OSTEOSARCOMA
 begin in intramedullary location – break
through cortex - form a soft tissue mass.
 histologi...
RADIOGRAPH showing typical malignant features including permeative-motheaten
pattern of destruction, irregular cortical de...
Radiological Features
•Plain radiographs are most valuable tool for correct
diagnosis
•Most common is – aggressive lesion ...
OSTEOID MATRIX
Cloud-like bone formation in
osteosarcoma.
Notice the aggressive, interrupted
periosteal reaction
Trabecula...
Wide zone of transition indicates malignancy or infection or
eosinophilic granuloma
An ill-defined border with a broad zon...
PERIOSTEAL REACTION
non-specific reaction and will occur whenever
the periosteum is irritated by a malignant
tumor, benign...
PERIOSTEAL REACTION
 The periosteum is a membrane
several cell layers thick that covers
entire bone except area covered b...
PERIOSTEAL REACTION
 With slow-growing lesions, the
periosteum has time to produce new
bone
 With rapidly growing lesion...
PERIOSTEAL REACTION
 If the lesion grows rapidly but
steadily, the periosteum will not
have enough time to lay down
even ...
A benign type of periosteal reaction is a thick, wavy and uniform
callus formation resulting from chronic irritation.
Beni...
Aggressive periosteal reaction
Osteosarcoma with
interrupted periosteal
reaction and Codman's
triangle proximally.
Ewing s...
osteoid
osteoma
chr. Osteomyelitis
Ewing’
s
A)hair on end –
Ewing’s
B) Sunburst-
Osteosarcoma
Anteroposterior and lateral radiographs of
proximal tibia with chondroblastic
osteosarcoma.
CT scan
 the neoplastic bone appears amorphous .
 used to evaluate the chest for pulmonary metastases.
 approximately 1...
M R I
 largely replaced ct as the optimal modality for
imaging the primary tumor.
 demonstrates the degree of soft tissu...
Anteroposterior view of proximal humerus with
osteoblastic osteosarcoma.
MRI shows extent of tumor within bone and soft ti...
Bone scan
 bone scan with technetium 99m shows a marked increase in the
uptake due to active formation of new tumor and h...
• gallium scans
are the most sensitive tests for locating
nonpulmonary metastases.
• positron emission tomography
• useful...
BIOPSY
single most important step in
- staging,
- histological diagnosis and
- to plan type and extent of treatment.
TYPES
Incisional biopsy-
- Less sampling error,
- provides the most tissue for additional diagnostic
studies, such as cyto...
Needle biopsy
• may be 90% accurate at determining
malignancy; however, its accuracy at determining
specific tumor type is...
BIOPSY PRECAUTIONS
• Placement of the biopsy is a crucial decision because the
biopsy track needs to be excised en bloc wi...
•The deep incision should go through a single
muscle compartment rather than contaminating
an intermuscular plane
The peri...
If hole must be made in bone during biopsy, defect should be round to
minimize stress concentration, which otherwise could...
poorly performed biopsies.
Biopsy resulted in irregular defect in bone, which led to pathological fracture.
Transverse inc...
Needle biopsy track
contaminated patellar
tendon.
Drain site was not
placed in line with
incision.
STAGING of
Osteosarcoma
Enneking System for Staging
Malignant Tumors
Stage Grade Site Metastases
IA Low Intracompartmental None
IB Low Extracompar...
American Joint Committee on Cancer
System for Staging Soft-Tissue
Sarcomas
Stage Grade Size Depth Metastases
I Low Any Any...
TNM STAGING OF BONE TUMORS
Lab investigations
 CBC - usually normal
 ESR - elevated, not specific.
 ALP - elevated in osteosarcoma, reflecting
ost...
 the course of osteosarcoma can be monitored by serial
determination of serum alkaline phosphatase levels.
 following ab...
PERIOSTEAL OSTEOSARCOMA
 an intermediate-grade chondroblastic
osteosarcoma that arises on the surface of the
bone.
 the ...
PAROSTEAL OSTEOSARCOMA
 low grade fibroblastic or juxtracortical
osteosarcoma.
 4 % of all osteosarcoma.
 occurs at lat...
• it usually appears on the surface ( rather than
intracortically ) producing large homogeonenous
lobulated new bone outsi...
D/D
• osteochondroma-
shows a medullary cavity containing marrow in
continuity with the medullary canal of the
involved bo...
LOW-GRADE INTRAMEDULLARY
OSTEOSARCOMA
• rare type
• an indolent course with relatively benign features on
radiograph.
• mi...
prognosis
 GENERAL PROGNOSIS IS BETTER THAN
CONVENTIONAL OS
 PRI. AMPUTATION – 50 – 70 % 5 YR
SURVIVAL
 FOR SMALL LESIO...
HIGH-GRADE SURFACE
OSTEOSARCOMA
• least common type.
• an aggressive tumor arising on the outer aspect of
the cortex.
• ra...
TELANGIECTACTIC OSTEOSARCOMA
• purely lytic
• x-ray may show invasive lesion or ballooned out
appearance similar to ABC
• ...
SMALL CELL OSTEOSARCOMA
 high grade lesion
 consists of blue cells resembling ewing’s
sarcoma or lymphoma
 cytogenetic ...
SECONDARY OSTEOSARCOMA
• rare in young but constitutes almost of the
osteosarcomas in pts. older then 50 yrs of age.
• mos...
a Resection of proximal tibia with typical features of osteosarcoma.
Mapping of the specimen is done in order to evaluate ...
• other conditions
 fibrous dysplasia
 bony infarcts
 osteochondromas
 chronic osteomyelitis
 dedifferentiated chondr...
CHEMOTHERAPY
• ADJUVANT CHEMOTHERAPY -chemotherapy administered
postoperatively to treat presumed micrometastases.
• neoad...
 chemotherapy drugs are most effective when the
tumor against which they are directed is small.
 combinations of these d...
Advantages of neoadjuvant
chemotherapy over adjuvant
chemotherapy. Preoperative chemotherapy frequently causes regression...
Preoperative chemotherapy theoretically may
decrease the spread of tumor cells at the time of
surgery.
neoadjuvant chemo...
CHEMOTHERAPEUTIC AGENTS
 DOXORUBICIN
 Glycoside antibiotic,binds to DNA and inhibits
RNA synthesis.
 Toxic effects-
 R...
METHOTREXATE
 Binds to di-hydro folate reductase and cessation
of DNA synthesis
 Dose-
 Vincristine is given 2 mg/sq m...
CHEMOTHERAPY REGIMEN
 Doxorubicin and cisplatin therapy
 Doxorubicin 25 mg/m2 IV on days 1-3 plus cisplatin 100
mg/m2 IV...
Chemotherapy contd
 Adjuvant
 High-dose methotrexate 12 g/m2 IV given over 4h on
weeks 3, 4, 8, 9, 13, 14, 18, 19,23, 24...
 Doxorubicin, cisplatin, ifosfamide, and high-
dose methotrexate
Ifosfamide 15 g/m2 plus methotrexate 12 g/m2plus
cispla...
PRINCIPLES OF SURGERY
 Amputation versus Limb Salvage
 Simon described four issues that must be considered whenever
cont...
AMPUTATION
Irrespective of the method chosen to treat
osteosarcoma, the local tumor must be
completely excised with negat...
Indications for amputation
 very young age, when limb length inequality would be a major
problem
 displaced pathologic f...
 The level of amputation is determined by close scrutiny of
conventional radiographs, bone scans, and MRI.
 The entire i...
 In very young children, residual limb overgrowth may be a
problem.
 For below-knee amputations, this can be addressed b...
 In “expendable” bones such as the clavicle, fibula, scapula, and
rib, resection without reconstruction can be considered...
 For lesions of the extremities that are deemed resectable, the
reconstruction can be complex and depends on the age of t...
SALVAGE V/S AMPUTATIUON
 more extensive surgical procedure
 greater amount of morbidity
 multiple future operations
 p...
 durability of reconstructions in long term
survivors
 none of the reconstruction will give normal
function
 ultimately...
 Limb salvage –
 is considered if there has been no progression of disease
locally or distantly and if the nerves and bl...
BARRIERS TO LIMB SALVAGE
 poorly placed biopsy incision
 major vascular involvement
 encasement of major motor nerve
 ...
PHASES OF LIMB SALVAGE
 RESECTION OF TUMOR
 SKELETAL RECONSTRUCTION
 SOFT TISSUE AND MUSCLE TRANSFER
“THREE STRIKE RULE”
SURGICAL
MARGIN
An intralesional margin --plane of surgical
dissection is within the tumor.
A marginal margin --closest plane of
dissectio...
Resections and
reconstructions currently, most musculoskeletal malignancies are
treated local resection and reconstructio...
 reconstructions often are done on young patients
who are extremely active.
 most reconstructions involve preserving a m...
RECONSTRUCTION OF BONE DEFECT
A. SPONTANEOUS REPAIR
B. BONE GRAFTING
C. PROSTHETIC REPLACEMENT
D. COMBINATION OF ABOVE
SPONTANEOUS REPAIR
A. is synonymous with fracture healing
B. small cavities produced by subtotal
curettage
C. defects foll...
BONE GRAFTING
A. AUTOGENOUS-
 CANCELLOUS
 CORTICAL
 COMBINED
 AUTOCLAVED
 VASCULARISED
AUTOCLAVED AUTOGRAFTS
 tumor and bone are excised, majority of lesion is
removed from bone and remaining bone is
autoclav...
OSTEOARTICULAR ALLOGRAFTS
 ADVANTAGES
 ability to replace ligaments, tendons, and
intraarticular structures
 Complicati...
Osteoarticular allografts may have a role as a
temporary measure to preserve an adjacent
physis in an immature patient
A p...
ALLOGRAFT-PROSTHESIS COMPOSITES
 may provide a long-term solution for some
patients.
 avoid the complications of degener...
 main indication for an allograft-
prosthesis composite
is an inadequate length of
remaining host bone to secure
the stem...
ENDOPROSTHETIC RECONSTUCTION
 provide long-term function for some patient
advantage
 predictable immediate stability tha...
long-term complications
polyethylene wear is still a limiting factor for
articulating surfaces
 fatigue fracture can occ...
 For patients who are near skeletal maturity
1) the reconstructed limb can be lengthened 1 cm at the initial
procedure.
...
distal femur of 7-year-old girl with telangiectatic osteosarcoma. C,
Intraoperative photograph of resected specimen and cu...
Repiphysis lengthening procedure. A, Locking mechanism (arrow) located.
B, The patient's leg is marked at this site. C, El...
• Rotationplasty is a procedure which allows the ankle to
substitute as the knee after 180 degree rotation of the limb.
•T...
 Winkelmann classified rotationplasty into five groups, as
follows:
GROUP AI - lesion in distal femur.
the distal femur, ...
GROUP AII
 lesion in the proximal tibia.
 distalmost femur, knee joint, and
proximal tibia are resected.
 after rotatio...
  GROUP BI
• lesion in the proximal femur sparing the hip joint
and gluteal muscles.
• the upper femur and hip joint are r...
ROTATIONPLASTY CONTD..
 GROUP BII —lesion in the proximal femur with
involvement of hip joint and contiguous soft
tissue....
GROUP BIII. – lesion in mid femur
the entire femur is resected.
the tibia is attached to the pelvis using
an endoprosthesis
Long term prognosis
 In patients who are long-term survivors after resection
of an extremity sarcoma, the probability of ...
Regarding prosthetic or allograft-prosthetic composite
reconstructions
location is the most important issue proximal
reco...
RADIOTHERAPY
Osteosarcoma is a relatively radioresistant malignancy.
For this reason, adjuvant chemotherapy and surgery h...
 modern radiation delivery techniques such as
intensity modulated radiation therapy and proton
beam therapy can be used.
...
BRACHYTHERAPY
 hollow catheters are implanted in the tumor bed at the
time of resection.
 These catheters exit through t...
Brachytherapy catheters woven through polyglactin 910 (Vicryl) mesh to
help maintain proper spacing. Catheters placed alon...
Megavoltage radiotherapy
 principle
1. radical dose levels of 7000 – 8000 rads.
2. distribute the dose according to proba...
 HIGH TUMOR DOSE OF 6000- 7000 RADS
(SOMETIMES 8000 RADS)
 230 RADS/DAY OR 1000 RADS/WKLY.
 PRECAUTIONS-
 WHEN BIOPSY ...
Newer agents
 liposomal muramyl tripeptide-phosphatidyl-
ethanolamine(mifamurtide)- an agent derived from
BCG that activa...
prognosis
• most series report long-term survival of
60% to 75% for patients with high-grade
osteosarcoma without metastas...
Prognostic factors
1. THE EXTENT OF THE DISEASE.(MOST
IMPORTANT )
2. GRADE OF LESION
3. SIZE OF PRIMARY TUMOR
4. SKELETAL ...
THANK YOU
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Osteosarcoma ppt

  1. 1. CHAIRPERSON- DRVENKATESH MULIMANI SPEAKER- DRVEERESH M OSTEOSARCOMA
  2. 2. OSTEOSARCOMA
  3. 3. Osteosarcoma  Malignant tumor characterized by production of osteoid by malignant cells.  composed of sarcomatous stroma & malignant osteoblasts that directly form tumor osteoid , although fibrous or cartilagenous elements coexists or predominate.  arises in the metaphysis of long bone where normally growth is more active.
  4. 4. • 2nd m.c primary malignancy of the bone • most common malignant tumor of bone in children & young adult • accounts for 20% of primary malignacies of the bone • incidence 1 to 3 per 1 million per year
  5. 5.  all skeletal locations can be affected ; however, most primary osteosarcomas occur at the sites of the most rapid bone growth.  most common sites are  the distal end of femur  the proximal end of tibia (accounts for more than 50 % of cases)  the proximal end of humerus  the proximal end of femur.
  6. 6. most common sites
  7. 7. 10 20 30 40 50 60 70 yrs Osteogenic Sarcoma
  8. 8.  may affect any age.  Generally between 10- 25 yrs.  primary high-grade osteosarcoma - second decade of life.  parosteal osteosarcoma - peak incidence in the third and fourth decades.  secondary osteosarcomas - in older individuals  male > female except parosteal osteosarcoma which is more common in females
  9. 9. ETIOLOGY  Oncogenic viruses like Harvey and Moloney mouse sarcoma virus(RNA virus) and polyoma and SV 40 (DNA virus)  Radiation exposure above 2000 rads with latent period of 4 yrs.  Chemical agents like 20-methyl cholanthrene,beryllium compounds.
  10. 10. Clinical features • Symptoms 1)Progressive pain- results from microinfarctions . 2)night pain only about 25% of patients experience this phenomenon 3)Swelling appears after a few days & progressively increases 4) An antalgic limp 5) Great majority of patients do not have fever, wt loss, cachexia, except for disease at primary site
  11. 11. SIGNS  fusiform swelling  consistency : variegated  dilated veins  skin stretched and shiny  local rise of temperature tenderness pulmonary signs with metastasis
  12. 12. GROSS APPEARANCE  Situated in metaphysis of long bones (lower end of femur,upper end of tibia and humerus)  Appears as large tumor with destruction of inner cortex as it extends into subperiosteal space.  Stony hard to soft,gritty consistency  Color reflects its components-fibrous looks white,osseous-yellowish white,cartilagenous- bluish white.  Necrotic foci and areas of degeneration are seen
  13. 13. Pathological Features • ‘Mutton leg’ appearance • Grayish white • Edge stops at epiphyseal cartilage
  14. 14. Microsopy • primarily osteoblastic, fibroblastic, or chondroblastic • spindle cells • malignant osteoid producing cells • variable appearance polyhedral/round/ cuboidal / columnar • intense hypercellularity, • abundant mitotic figures, • marked nuclear pleomorphism
  15. 15. • intercellular matrix scanty/ considerable amount • myxomatous/cartilagenous/ osseous • osteoclastic cell type – when there is rapid destruction of the bone. • cartilage cells- chondroblastic osteosarcoma
  16. 16. TYPES • PRIMARY OSTEOSARCOMA  CONVENTIONAL OSTEOSARCOMA ( HIGH – GRADE)  PERIOSTEAL OSTEOSARCOMA  PAROSTEAL OSTEOSARCOMA  LOW-GRADE INTRAMEDULLARY OSTEOSARCOMA  HIGH-GRADE SURFACE OSTEOSARCOMA  TELANGIECTATIC OSTEOSARCOMA  SMALL CELL OSTEOSARCOMA • SECONDARY OSTEOSARCOMA
  17. 17. CONVENTIONAL OSTEOSARCOMA  begin in intramedullary location – break through cortex - form a soft tissue mass.  histologically – osteoblastic/ fibroblastic / chondroblastic  osteoid production from tumor cells.  high grade spindle cell component.
  18. 18. RADIOGRAPH showing typical malignant features including permeative-motheaten pattern of destruction, irregular cortical destruction and aggressive (interrupted) periosteal reaction.
  19. 19. Radiological Features •Plain radiographs are most valuable tool for correct diagnosis •Most common is – aggressive lesion in the metaphysis of long bone(90%).( 10% diaphyseal & 1% epiphyseal) •Predominantly blastic / lytic •Lesions are quite permeative & ill defined •Codman’s triangle, Sunburst / hair on end appearance may be seen.
  20. 20. OSTEOID MATRIX Cloud-like bone formation in osteosarcoma. Notice the aggressive, interrupted periosteal reaction Trabecular ossification pattern in osteoid osteoma. Notice osteolytic nidus (arrow).
  21. 21. Wide zone of transition indicates malignancy or infection or eosinophilic granuloma An ill-defined border with a broad zone of transition is a sign of aggressive growth It is a feature of malignant bone tumors. There are two tumor-like lesions which may mimic a malignancy and have to be included in the differential diagnosis. These are infections and eosinophilic granuloma
  22. 22. PERIOSTEAL REACTION non-specific reaction and will occur whenever the periosteum is irritated by a malignant tumor, benign tumor, infection or trauma two patterns of periosteal reaction: a benign and an aggressive type.
  23. 23. PERIOSTEAL REACTION  The periosteum is a membrane several cell layers thick that covers entire bone except area covered by cartilage.  Besides covering the bone and sharing some of its blood supply with the bone, it also produces bone when it is stimulated appropriately 25
  24. 24. PERIOSTEAL REACTION  With slow-growing lesions, the periosteum has time to produce new bone  With rapidly growing lesions, the periosteum cannot produce new bone as fast. An interrupted pattern results, which may be:  a thin shell of calcified new bone  one or more concentric shells of new bone over the lesion, sometimes called lamellated or "onion-skin" periosteal reaction. 26
  25. 25. PERIOSTEAL REACTION  If the lesion grows rapidly but steadily, the periosteum will not have enough time to lay down even a thin shell of bone  In such cases, the tiny fibers that connect the periosteum to the bone (Sharpey's fibers) become stretched out perpendicular to the bone.  When these fibers ossify, they produce a pattern sometimes called "sunburstsunburst" or "hair-on-hair-on- endend" periosteal reaction, depending of how much of the bone is involved by the process. 27
  26. 26. A benign type of periosteal reaction is a thick, wavy and uniform callus formation resulting from chronic irritation. Benign periosteal reaction in an osteoid osteoma
  27. 27. Aggressive periosteal reaction Osteosarcoma with interrupted periosteal reaction and Codman's triangle proximally. Ewing sarcoma with lamellated and focally interrupted periosteal reaction Infection with a multilayered periosteal reaction
  28. 28. osteoid osteoma chr. Osteomyelitis Ewing’ s A)hair on end – Ewing’s B) Sunburst- Osteosarcoma
  29. 29. Anteroposterior and lateral radiographs of proximal tibia with chondroblastic osteosarcoma.
  30. 30. CT scan  the neoplastic bone appears amorphous .  used to evaluate the chest for pulmonary metastases.  approximately 10% to 20% of patients with osteosarcoma present with radiographically detectable metastases at diagnosis. most of these are in the lungs.  chest ct is superior to plain radiography in demonstrating these metastases, and spiral ct is superior to conventional ct for this purpose.
  31. 31. M R I  largely replaced ct as the optimal modality for imaging the primary tumor.  demonstrates the degree of soft tissue extension and the relationship of the extracompartmental tumor to fascial planes and neurovascular structures.  best feature is its ability to precisely evaluate the extent of tumor in the medullary cavity.  occult skip metastases of 2 mm or more in long bones are well seen on MRI
  32. 32. Anteroposterior view of proximal humerus with osteoblastic osteosarcoma. MRI shows extent of tumor within bone and soft tissue better.
  33. 33. Bone scan  bone scan with technetium 99m shows a marked increase in the uptake due to active formation of new tumor and host bone as well as the vascularity of the lesion.  radionuclide bone scintigraphy is used to look for bony metastases in the involved bone (skip metastases) and at other skeletal sites.  mineralized metastases are more likely to be detected by bone scans than are nonmineralized ones at extrapulmonary sites.  the intensity of the uptake increases with the vascularity of the lesion.
  34. 34. • gallium scans are the most sensitive tests for locating nonpulmonary metastases. • positron emission tomography • useful in -staging, - planning the biopsy, - evaluating the response to chemotherapy, and helping to direct subsequent treatment.
  35. 35. BIOPSY single most important step in - staging, - histological diagnosis and - to plan type and extent of treatment.
  36. 36. TYPES Incisional biopsy- - Less sampling error, - provides the most tissue for additional diagnostic studies, such as cytogenetics and flow cytometry. - complication rates are high. core biopsy- - can provide an accurate diagnosis in 90% of cases. - the limited amount of tissue obtained may not be adequate excisional biopsy- done in benign tumors.
  37. 37. Needle biopsy • may be 90% accurate at determining malignancy; however, its accuracy at determining specific tumor type is much lower. • the absence of malignant cells on fine needle aspiration is less reassuring than a negative incisional biopsy
  38. 38. BIOPSY PRECAUTIONS • Placement of the biopsy is a crucial decision because the biopsy track needs to be excised en bloc with the tumor • Transverse incisions should be avoided because they are extremely difficult or impossible to excise with the specimen.
  39. 39. •The deep incision should go through a single muscle compartment rather than contaminating an intermuscular plane The periphery of a lesion usually contains the most viable tissue and is the best tissue on which diagnosis is based
  40. 40. If hole must be made in bone during biopsy, defect should be round to minimize stress concentration, which otherwise could lead to pathological fracture.
  41. 41. poorly performed biopsies. Biopsy resulted in irregular defect in bone, which led to pathological fracture. Transverse incisions should not be used. Multiple needle tracks contaminate quadriceps
  42. 42. Needle biopsy track contaminated patellar tendon. Drain site was not placed in line with incision.
  43. 43. STAGING of Osteosarcoma
  44. 44. Enneking System for Staging Malignant Tumors Stage Grade Site Metastases IA Low Intracompartmental None IB Low Extracompartmental None IIA High Intracompartmental None IIB High Extracompartmental None III Any Any Regional or distant metastases
  45. 45. American Joint Committee on Cancer System for Staging Soft-Tissue Sarcomas Stage Grade Size Depth Metastases I Low Any Any None II Low ≤5 cm Any None High >5 cm Superficial None III High >5 cm Deep None IV Any Any Any Regional or distant
  46. 46. TNM STAGING OF BONE TUMORS
  47. 47. Lab investigations  CBC - usually normal  ESR - elevated, not specific.  ALP - elevated in osteosarcoma, reflecting osteogenesis in the neoplastic tissue. degree of elevation of this enzyme depend on activity of the neoplastic osteoblasts within the lesion and size of the tumor.  an elevated ALP level has been associated with a worse prognosis.
  48. 48.  the course of osteosarcoma can be monitored by serial determination of serum alkaline phosphatase levels.  following ablation of the tumor, the enzyme level falls to near normal; it rises with the development of metastases and with recurrence.  in some studies, the LDH level has been shown to be of prognostic importance.  an ELEVATED LDH level is associated with a worse prognosis
  49. 49. PERIOSTEAL OSTEOSARCOMA  an intermediate-grade chondroblastic osteosarcoma that arises on the surface of the bone.  the most common locations are the diaphysis of femur and tibia  it occurs in a slightly older and broader age group.  histological examination strands of osteoid-producing spindle cells radiating between lobules of cartilage.
  50. 50. PAROSTEAL OSTEOSARCOMA  low grade fibroblastic or juxtracortical osteosarcoma.  4 % of all osteosarcoma.  occurs at late age , females  slow growing  arises from surface of the bone  it invade the medullary cavity in the late stages  it has a peculiar tendency to occur as a lobulated ossified mass on the posterior aspect of the distal femur.
  51. 51. • it usually appears on the surface ( rather than intracortically ) producing large homogeonenous lobulated new bone outside the bone shell and into the soft tissue- often palpable. • histologically trabeculae of malignant bone & osteoid tissue with definite malignant connective tissue stroma, encapsulated by fibrous tissue.
  52. 52. D/D • osteochondroma- shows a medullary cavity containing marrow in continuity with the medullary canal of the involved bone • myositis ossificans- the ossification in myositis ossificans is more mature at the periphery of the lesion, whereas the center of a parosteal osteosarcoma is more heavily ossified
  53. 53. LOW-GRADE INTRAMEDULLARY OSTEOSARCOMA • rare type • an indolent course with relatively benign features on radiograph. • mistaken radiographically and histologically for an osteoblastoma or fibrous dysplasia. • located in an intramedullary location and erodes through the cortex only very late. • histologically slightly atypical spindle cells producing slightly irregular osseous trabeculae.
  54. 54. prognosis  GENERAL PROGNOSIS IS BETTER THAN CONVENTIONAL OS  PRI. AMPUTATION – 50 – 70 % 5 YR SURVIVAL  FOR SMALL LESIONS, EARLY WIDE RESECTIONS SHOW 80 – 90 % LONG TERM SURVIVAL.
  55. 55. HIGH-GRADE SURFACE OSTEOSARCOMA • least common type. • an aggressive tumor arising on the outer aspect of the cortex. • radiographs show an invasive lesion with ill-defined borders. • the microscopic appearance is similar to conventional osteosarcoma. • in contrast to parosteal osteosarcoma, medullary involvement is common at the time of diagnosis.
  56. 56. TELANGIECTACTIC OSTEOSARCOMA • purely lytic • x-ray may show invasive lesion or ballooned out appearance similar to ABC • grossly , resembles a blood filled cyst with very small solid portion • on low power microscope it resembles ABC with blood filled spaces separated by septa but high power will reveal that cells in the septa are frankly malignant.
  57. 57. SMALL CELL OSTEOSARCOMA  high grade lesion  consists of blue cells resembling ewing’s sarcoma or lymphoma  cytogenetic and immunohistochemistry needed to differentiate them.
  58. 58. SECONDARY OSTEOSARCOMA • rare in young but constitutes almost of the osteosarcomas in pts. older then 50 yrs of age. • most common factors associated with it are 1. paget disease 2. previous radiation treatment • pagets osteosar. -6th – 8th decade of life and pelvis is the mc site. • radiation osteos. occurs in pts who have been treated with greater then 2500 cgy and occurs in unusal locations like skull, spine, clavicle, ribs, scapula and pelvis
  59. 59. a Resection of proximal tibia with typical features of osteosarcoma. Mapping of the specimen is done in order to evaluate the response to given preop chemotherapy. b Pretreatment biopsy of high-grade osteoblastic osteosarcoma. c After treatment the tumor is replaced by a network of acellular mineralized bone indicating good response. d Active fracture callus may show features resembling osteosarcoma but lack true anaplasia. e Resection of lower leg showing a telangiectatic osteosarcoma in the distal tibia. f Telangiectatic osteosarcoma resembles an aneurysmal bone
  60. 60. • other conditions  fibrous dysplasia  bony infarcts  osteochondromas  chronic osteomyelitis  dedifferentiated chondrosarcomas  osteogenesis imperfecta
  61. 61. CHEMOTHERAPY • ADJUVANT CHEMOTHERAPY -chemotherapy administered postoperatively to treat presumed micrometastases. • neoadjuvant chemotherapy chemotherapy administered before surgical resection of the primary tumor  currently most orthopaedic oncologists favor preoperative chemotherapy with the definitive procedure performed 3 to 4 weeks after the last dose has been administered.   chemotherapy is restarted 2 weeks postoperatively if the wound has healed. TREATMENT
  62. 62.  chemotherapy drugs are most effective when the tumor against which they are directed is small.  combinations of these drugs are more effective than single agents.  dosage, sequence of drugs, and schedule seem to be important in achieving the maximal response.  all have toxicity for normal tissues
  63. 63. Advantages of neoadjuvant chemotherapy over adjuvant chemotherapy. Preoperative chemotherapy frequently causes regression of the primary tumor, making a successful limb salvage operation easier.  . Neoadjuvant chemotherapy followed by surgical resection allows for histological evaluation of the effectiveness of treatment.  This is one of the most valuable prognostic indicators of successful long-term outcome.
  64. 64. Preoperative chemotherapy theoretically may decrease the spread of tumor cells at the time of surgery. neoadjuvant chemotherapy usually can be started immediately, effectively treating micrometastases at the earliest time possible.  Prevents tumor progression, which may occur during any delay before surgery.
  65. 65. CHEMOTHERAPEUTIC AGENTS  DOXORUBICIN  Glycoside antibiotic,binds to DNA and inhibits RNA synthesis.  Toxic effects-  Reversible and dose related are leukemia,transient alopecia,cardiomyopathy.  Dose-30 mg/sq mt BSA for 3 days,repeated every 4 wks,6 cycles.
  66. 66. METHOTREXATE  Binds to di-hydro folate reductase and cessation of DNA synthesis  Dose-  Vincristine is given 2 mg/sq m I.V half an hour before methotrexate as it promotes its uptake.  Methotrexate(1.5 gm/sq m) given as I.V infusion over 6 hr.  Repeated every 2 weekly and dose is gradually increased upto 7.5 gm/sq m  Toxic effects-bone marrow suppression,oral mucositis,vomiting and transient elevation of liver enzymes,candida superinfection.
  67. 67. CHEMOTHERAPY REGIMEN  Doxorubicin and cisplatin therapy  Doxorubicin 25 mg/m2 IV on days 1-3 plus cisplatin 100 mg/m2 IV on day 1; repeat cycle every 21 days.  High-dose methotrexate, cisplatin, and doxorubicin regimen  Neoadjuvant setting:  High-dose methotrexate 12 g/m2 IV given over 4h on weeks 0, 1, 5, 6, 13, 14, 18,19, 23, 24, 37, and 38, alternating with cisplatin 60 mg/m2 IV plus doxorubicin 37.5 mg/m2/day IV for 2d each on weeks 2, 7, 25, and 28.
  68. 68. Chemotherapy contd  Adjuvant  High-dose methotrexate 12 g/m2 IV given over 4h on weeks 3, 4, 8, 9, 13, 14, 18, 19,23, 24, 37, and 38, alternating with cisplatin 60 mg/m2 IV plus doxorubicin 37.5 mg/m2/day IV for 2d each on weeks 5, 10, 25, and 28  2 cycles are given preoperatively, and 4 cycles are usually given postoperatively  Requires administration of 15 mg leucovorin every 6h for 10 doses, starting 24h after initiation of high dose
  69. 69.  Doxorubicin, cisplatin, ifosfamide, and high- dose methotrexate Ifosfamide 15 g/m2 plus methotrexate 12 g/m2plus cisplatin 120 mg/m2plus doxorubicin 75 mg/m2 Postoperatively, patients receive 2 cycles of doxorubicin 90 mg/m2 and 3 cycles each of high-dose ifosfamide, methotrexate, and cisplatin 120-150 mg/m2 Granulocyte colony-stimulating factor (G-CSF) support is mandatory after the high-dose
  70. 70. PRINCIPLES OF SURGERY  Amputation versus Limb Salvage  Simon described four issues that must be considered whenever contemplating limb salvage instead of an amputation, as follows:  1. Would survival be affected by the treatment choice?  2. How do the short-term and long-term morbidity compare?  3. How would the function of a salvaged limb compare with that of a prosthesis?  4. Are there any psychosocial consequences?
  71. 71. AMPUTATION Irrespective of the method chosen to treat osteosarcoma, the local tumor must be completely excised with negative margins. Although amputation is performed less frequently than in the past, it remains the gold standard of local control.
  72. 72. Indications for amputation  very young age, when limb length inequality would be a major problem  displaced pathologic fractures  large soft tissue masses involving neurovascular structures; disease progression during chemotherapy;  local recurrence following limb salvage procedures.  In the upper extremity, attempt is made to preserve at least hand function, because prosthetic replacements are not nearly as good as a functional hand.  However, in the lower extremity, modern prosthetics are very functional.
  73. 73.  The level of amputation is determined by close scrutiny of conventional radiographs, bone scans, and MRI.  The entire involved bone should be carefully evaluated by MRI for skip metastases.  Most frequently, a wide cross-bone amputation is performed rather than a radical amputation.  Exceptions might be a young child with a tibial osteosarcoma, in whom knee disarticulation or above-knee amputation is performed, or a hindfoot osteosarcoma requiring a below-knee amputation.
  74. 74.  In very young children, residual limb overgrowth may be a problem.  For below-knee amputations, this can be addressed by placing a metacarpal plug in the distal tibial canal if the ipsilateral foot is uninvolved by tumor.  Further, in very young children, the predicted length of the residual limb at maturity may be very short if a growth plate is resected.  For foot tumors, this can be addressed with a Syme's-type amputation rather than a below-knee amputation  in proximal tibial lesions, a knee disarticulation may be preferable to an above-knee amputation. These can be revised at maturity if necessary for prosthetic fitting.
  75. 75.  In “expendable” bones such as the clavicle, fibula, scapula, and rib, resection without reconstruction can be considered.  Lesions of the radius and ulna are rare and can usually be resected with minimal reconstruction or with fibular autografts or allografts used for reconstruction.  Lesions of the hands and feet usually require amputation, although ray amputation and partial amputations that preserve some hand or foot function can sometimes be performed.
  76. 76.  For lesions of the extremities that are deemed resectable, the reconstruction can be complex and depends on the age of the patient and the location of the tumor in reference to joints and growth plates.  For most distal femoral and proximal tibial osteosarcomas, an intracompartmental, intra-articular resection can be carried out.  The same is usually possible for lesions of the proximal humerus.  Reconstruction is achieved either with an osteoarticular allograft or with a metallic prosthesis.
  77. 77. SALVAGE V/S AMPUTATIUON  more extensive surgical procedure  greater amount of morbidity  multiple future operations  periprosthetic fractures, prosthetic loosening, allograft fracture, length discrepancy and late infection.  after initial salvage 33% may later have amputation
  78. 78.  durability of reconstructions in long term survivors  none of the reconstruction will give normal function  ultimately choice depends upon patient’s expectations and quality of life
  79. 79.  Limb salvage –  is considered if there has been no progression of disease locally or distantly and if the nerves and blood vessels are free of tumor.  The most important issue is the ability to completely resect the tumor with wide margins. The adjacent joint and growth plates are assessed for tumor involvement.  The thickness of the soft tissue margin depends on the type of tissue. A fascial margin is considered a more substantial barrier to tumor spread than a similar thickness of fat.  The resection should be planned with the goal of achieving local control; reconstruction options are a secondary consideration
  80. 80. BARRIERS TO LIMB SALVAGE  poorly placed biopsy incision  major vascular involvement  encasement of major motor nerve  pathological fracture of involved bone
  81. 81. PHASES OF LIMB SALVAGE  RESECTION OF TUMOR  SKELETAL RECONSTRUCTION  SOFT TISSUE AND MUSCLE TRANSFER “THREE STRIKE RULE”
  82. 82. SURGICAL MARGIN
  83. 83. An intralesional margin --plane of surgical dissection is within the tumor. A marginal margin --closest plane of dissection passes through the pseudocapsule. Wide margins --plane of dissection is in normal tissue Radical margins --all the compartments that contain tumor are removed en bloc
  84. 84. Resections and reconstructions currently, most musculoskeletal malignancies are treated local resection and reconstruction.  goal of resection -- is to achieve wide surgical margins if possible.  if this is impossible because of anatomical constraints, a marginal resection combined with adjuvant or neoadjuvant treatment (e.g., radiation for a soft-tissue sarcoma) may be preferable to an amputation  a marginal resection usually is adequate for most benign neoplasms
  85. 85.  reconstructions often are done on young patients who are extremely active.  most reconstructions involve preserving a mobile joint, for which these general options are available:  osteoarticular allograft reconstruction,  endoprosthetic reconstruction,  allograft-prosthesis composite reconstruction.  rotationplasty
  86. 86. RECONSTRUCTION OF BONE DEFECT A. SPONTANEOUS REPAIR B. BONE GRAFTING C. PROSTHETIC REPLACEMENT D. COMBINATION OF ABOVE
  87. 87. SPONTANEOUS REPAIR A. is synonymous with fracture healing B. small cavities produced by subtotal curettage C. defects following wide or marginal excision(stability provided by remaining bone and internal fixation)
  88. 88. BONE GRAFTING A. AUTOGENOUS-  CANCELLOUS  CORTICAL  COMBINED  AUTOCLAVED  VASCULARISED
  89. 89. AUTOCLAVED AUTOGRAFTS  tumor and bone are excised, majority of lesion is removed from bone and remaining bone is autoclaved for 20mins.  advantage is easy to procure and absence of donor morbidity  disadvantage is high incidence of nonunion, fatigue failure and infection.
  90. 90. 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  failure of ligament and tendon attachments.
  91. 91. Osteoarticular allografts may have a role as a temporary measure to preserve an adjacent physis in an immature patient 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.
  92. 92. ALLOGRAFT-PROSTHESIS COMPOSITES  may provide a long-term solution for some patients.  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.  associated, however, with fatigue fracture, infection, and nonunion at the graft-host junction. .
  93. 93.  main indication for an allograft- prosthesis composite is an inadequate length of remaining host bone to secure the stem of an endoprosthesis.
  94. 94. ENDOPROSTHETIC RECONSTUCTION  provide long-term function for some patient advantage  predictable 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.
  95. 95. long-term complications polyethylene wear is still a limiting factor for articulating surfaces  fatigue fracture can occur at the rotating hinge, but this too is easily replaceable. fatigue fracture at the base of the intramedullary stem where it attaches to the body of the prosthesis is more problematic for pediatric patients, future limb-length inequality must be considered.
  96. 96.  For patients who are near skeletal maturity 1) the reconstructed limb can be lengthened 1 cm at the initial procedure. 2)epiphysiodesis of the contralateral limb can be done at the appropriate age to preserve limb-length equality (or to minimize inequality).  For younger patients,  amputation and rotationplasty  repiphysis expandable prosthesis
  97. 97. distal femur of 7-year-old girl with telangiectatic osteosarcoma. C, Intraoperative photograph of resected specimen and custom Repiphysis prosthesis. D, Intraoperative photograph after placement of prosthesis. E, Anteroposterior radiograph
  98. 98. Repiphysis lengthening procedure. A, Locking mechanism (arrow) located. B, The patient's leg is marked at this site. C, Electromagnetic coil is placed around the patient's leg at the level of the locking mechanism. D, Device activated. E and F, Preexpansion and postexpansion radiographs
  99. 99. • Rotationplasty is a procedure which allows the ankle to substitute as the knee after 180 degree rotation of the limb. •The original idea was conceived by Borggreve in 1927 to treat a shortened lower limb with stiff knee after tuberculosis . • Later popularized by Van Ness for management of proximal focal femoral deficiency. •Salzer in 1974 first used it for malignant tumors around the knee. ROTATIONPLASTY
  100. 100.  Winkelmann classified rotationplasty into five groups, as follows: GROUP AI - lesion in distal femur. the distal femur, knee joint, and proximal tibia are resected; the lower leg is rotated 180 degrees; tibia is joined to the remaining femur.  .
  101. 101. GROUP AII  lesion in the proximal tibia.  distalmost femur, knee joint, and proximal tibia are resected.  after rotation of 180 degrees, the distal tibia is joined to the distal femur
  102. 102.   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 .   
  103. 103. ROTATIONPLASTY CONTD..  GROUP BII —lesion in the proximal femur with involvement of hip joint and contiguous soft tissue.  upper femur, hip joint, and lower hemipelvis are resected, and the leg is rotated 180 degrees  remaining femur is joined to the remnant of the ilium so that the knee functions as a hinged hip joint and the ankle functions as the knee
  104. 104. GROUP BIII. – lesion in mid femur the entire femur is resected. the tibia is attached to the pelvis using an endoprosthesis
  105. 105. Long term prognosis  In patients who are long-term survivors after resection of an extremity sarcoma, the probability of limb survival is associated with  1) type of reconstruction  2) the location of the tumor.
  106. 106. Regarding prosthetic or allograft-prosthetic composite reconstructions location is the most important issue proximal reconstructions generally outlasting more distal reconstructions. (This is the inverse of the prognosis for overall patient survival, with distal sarcomas having a better prognosis than proximal sarcomas.) Proximal femoral reconstructions generally outlast distal femoral reconstructions, which generally outlast proximal tibial reconstructions
  107. 107. RADIOTHERAPY Osteosarcoma is a relatively radioresistant malignancy. For this reason, adjuvant chemotherapy and surgery have been the mainstays of therapy. Radiation therapy in the primary local control setting should be reserved on a case-by-case basis for patients with unresectable tumors and/or where margins of resection are positive .  Typically these tumors involve the head and neck or spinal region. For definitive radiation therapy, doses of 55–60 Gy are given with conventional daily fractionation of 1.8 Gy.
  108. 108.  modern radiation delivery techniques such as intensity modulated radiation therapy and proton beam therapy can be used.  Here the delivery of radiation to a target volume is improved while scatter to surrounding organs can be minimized.  Radiation therapy can be used as an effective palliative measure particularly for painful bony metastases.
  109. 109. BRACHYTHERAPY  hollow catheters are implanted in the tumor bed at the time of resection.  These catheters exit through the skin.  Postoperative radiographic evaluation and computer calculations determine the optimal loading of the catheters with radioisotopes.  High doses to be delivered to the target tissues.  The radiation levels fall off rapidly at the edges of the field, sparing normal tissues
  110. 110. Brachytherapy catheters woven through polyglactin 910 (Vicryl) mesh to help maintain proper spacing. Catheters placed along vessels and bone (where margins were close) exiting through separate stab wounds. soft-tissue sarcoma
  111. 111. Megavoltage radiotherapy  principle 1. radical dose levels of 7000 – 8000 rads. 2. distribute the dose according to probable disribution of tumor cells. 3. exclude all normal tissue and biopsy scar.  with proper treatment 1. painless & nonedematous limb is attained 2. reduced incidence of fibrotic, atrophic limb  disadvantage -pathological # can occcur.
  112. 112.  HIGH TUMOR DOSE OF 6000- 7000 RADS (SOMETIMES 8000 RADS)  230 RADS/DAY OR 1000 RADS/WKLY.  PRECAUTIONS-  WHEN BIOPSY IS DONE PRIOR TO FULL COURSE OF IRRADIATION - BIOPSY SCAR SHOULD BE HELD LESS THAN 2 CM. TO PREVENT RADIATION NECROSIS & SKIN BREAKDOWN FOLLOWED BY INF & HAEMORRHAGE.  NEEDLE BIOPSY SHOULD PREFERRED IN SUCH CASES.
  113. 113. Newer agents  liposomal muramyl tripeptide-phosphatidyl- ethanolamine(mifamurtide)- an agent derived from BCG that activates macrophages and increases circulating cytokine levels.  Transtuzumab (Herceptin)- a monoclonal antibody to HER2/erbB-2
  114. 114. prognosis • most series report long-term survival of 60% to 75% for patients with high-grade osteosarcoma without metastases at initial presentation and 90% for low-grade lesions.
  115. 115. Prognostic factors 1. THE EXTENT OF THE DISEASE.(MOST IMPORTANT ) 2. GRADE OF LESION 3. SIZE OF PRIMARY TUMOR 4. SKELETAL LOCATION 5. LOCAL RECURRENCE • POOR PROGNOSTIC FACTORS 1. RAPID RELAPSE AFTER COMPLETION OF INITIAL TREATEMENT 2. MANY, LARGE, UNRESECTABLE PULMONARY NODULES
  116. 116. THANK YOU

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