Osteosarcoma (Osteogenic sarcoma)

Defination:
Osteosarcoma can be defined as a malignant tumor of the bone in
which malignant mesenchymal tumor cells have the ability to
produce osteoid or mammalian bone

Classification of osteosarcoma:
A. According to nature of bone involved and site of origin
a. Primary osteosarcoma (2nd decade)
i. Intramedullary (Classical)
a. Conventional (based on histology)
i. Osteoblastic
ii. Chondroblastic
iii. Fibroblastic
b. Talengiectic
i. Large vascular channel
ii. Bone changes like ABC
iii. Most aggressive
c. Well differentiated (low grade)
ii. Intracortical
iii. Surface
a. Parosteal – from outer layer of
periosteum (juxta cortical)
b. Periosteal – from inner layer of
periosteum and outer layer of
cortex.
c. High grade surface (denovo and
differentiated)
b. Secondary osteosarcoma (5th decade)
i. Paget’s osteosarcoma – 1%
ii. Fibrous dysplasia
iii. Post irradiation
iv. Implant
v. Chronic osteomyelitis
B. Radiological classification
1. Sclerotic type
 Around puberty
 Dense irregular bone is seen at the
metaphysis
2. Osteolytic type
 Metaphyseal location
 Radiolucent gap is seen
 Increased density at edge
3. Mixed type
 Usually metaphyseal but frequently
seen on midshaft
4. Radiating spicule type
A. Least common variety,
 B. Occurs at puberty
C. Metaphyseal location is parallel & not
radiating, does not taper but remain of same
breath
C. Histological classification
a. Osteogenic osteosarcoma – if osteoid tissue is more
b. Chondrogenic osteosarcoma – if cartilage tissue is
more
c. Fibrogenic osteosarcoma – if fibrous tissue is more

Etiology of osteosarcoma:
A. Predisposing factors
1. Age – peak incidence 2nd decade, rare<10
year
2. Sex – Male > Female
3. Anatomical site – more thsn 90% in
metaphysis of long bone
a. Common sites –
i. Around knee (lower end femur –
50%,
upper end of tibia –
30%)
ii. Upper end of humerus – 10%
b. Less common –
i. Upper fibula
ii. Iliac bone
iii. Vertrebrae
iv. Jaw bone
v. Any other bones
4. Family history – more common with the
hereditary form of
 Retinoblastoma,
 Rothmund-Thomson
syndrome, and
 Li-Fraumeni syndrome
B. Exciting factors
a. Onchogenic viruses – DNA/RNA
b. Radiation – Localized radiation at a dose of >2000 rad
Latent period of 3-4 year
c. Chemicals – Beryllium compound
20 methyl cholanthrene

Clinical feature:
A. Symptom
a. Onset – is gradual and spontaneous
b. Pain – Usually the 1st symptom
i. Progressive intermittent at first
 ii. Then constant
iii. Gradually increase in severity
iv. Worse at night ( due to congestion)
c. Swelling /lump
d. Pathological fracture (some fast growing lytic tumors -
rare)
e. H/O trauma – precipitate or attention the lesion
f. May present with metastatic symptoms (pulmonary
symptom)
i. Chest pain
ii. Cough
iii. Haemoptysis
iv. Breathlessness
v. dyspnoea
g. Weak, cachexic and pseudoparalysis – in late stage

B. Sign
Early stage – mass is small, overlying tissue may normal
Late stage -
a. Look – Overlying skin – stretched, thin, glossy, never
ulcerated
b. Feel –
i. Tenderness – at the end of long bone
ii. Palpable mass –
a. Site – at the end of long bone
b. Size –
c. Shape – spindle
d. Consistency varies from stony hard to
soft
e. Ill defined margin
f. Raised local temperature
g. Engorged (dilated) vein
c. Move – Joint mobility is intact until epiphysis or muscle
not involved
Abnormal movement or crepitation- if pathological
fracture
d. Regional lymph node may enlarged

Investigation –
1. Blood biochemistry
i. Hb% - ↓ , ESR - ↑
ii. S. Alkaline phosphatase – markedly
increase
iii. LFT
iv. LDH – prognostic significance
2. Plain radiograph of affected part
i. Hazy osteolytic lesion may alternate with
unusually dense osteoblastic area
 ii. Endosteal margin is poorly defined/
eroded moath eaten appearance
iii. Cortex is breached and tumor extend to
adjacent tissue
iv. Sunburst appearance
v. Codman’s triangle
vi. Pathological fracture
3. X – ray chest – to see pulmonary metastases
4. USG of whole abdomen – to exclude
metastases
5. Bone scan – to show skip lesions
6. CT scan – to see extant of tumor, pulmonary
metastasis
7. MRI – to see extant of tumor
8. Biopsy – to confirm the diagnosis and
staging

Pathogenesis of osteosarcoma
1) Tumor starts at metaphysic and spread towards medullary
cavity, cortex & epiphysis
2) Skip lesion may occur in medulary cavity
3) Physis and articular cartilage both are resistant to spread
4) Extension towards cortex causes destruction of the cortex and
tumor comes to lie beneath periosteum
5) Newly formed neoplastic bone become perpendicular to the
surface of the shaft and along the newly formed blood vessel
producing “sun ray /sun blast” appearance.
6) Reactive subperiosteal bone is laid down and it is more
prominent in upper and lower angle (osteoperiosteal junction)
producing Codman’s triangle.
7) Ultimately periosteum breaks – tumor comes into soft tissue
8) Metastasis is early and haematogenous – producing
pulmonary deposit
9) Rarely early metastases to other bone suggest – multifocal
origin of sarcoma
Pathology:
A. Gross appearance/macroscopic
i. Location: Typically in the metaphysis
ii. Appearance: Large areas of bone destruction of
inner cortex
iii. Consistancy
 Various form stony hard to soft and
cystic
 More soft more aggressive
iv. Colours – depends on component
1. Fibrous – Grayish white F–G
2. Osseous – Yellowish white
C–B
3. Chondrogenic – Bluish white
v. Tumors contain large vascular channels and
haemorrhage
vi. Cystic cavitations are most pronounced in rapidly
growing tumor due to necrosis

B. Microscopic appearance
i. Stroma of spindle cells with the all
character of malignancy
 Anisocytosis
 poikilocytosis
 pleomorphism
 neuclear pyknosis
 polyhedral centricle, etc
ii. Central areas of tumor is most sclerotic
due to calcification of the necrotic tumor tissue
iii. Peripheral zone is suitable for biopsy –
where neoplastic tissue formation is prominent and
there is no calcification and necrosis
  Absolute criteria for diagnosis – sarcometus
stroma and direct formation of tumor osteiod and
bone by malignant C.T
 Some areas may have the characteristic
spindle cells with a pink-staining osteoid matrix;
 Others may contain cartilage cells or
fibroblastic tissue with little or no osteoid.
 Evidence of osteoid formation need special
attention

Treatment:
Aim:
1. Localization of tumor and
prevention of metastasis
2. Removal of tumor in ___ as early as
possible
3. Reconstruction of the affected part
or limb
4. Rehabilation of the patient

Principles of management of primary bone tumours:

i. High index of suspicion;
ii. Early referral to a tumour centre;
iii. Careful imaging studies;
iv. Biopsy after completion of imaging investigations;
v. Minimally invasive technique for biopsy;
vi. Multidisciplinary approach to management.

Protocol:
1. Preoperative staging and biopsy
confirmation
2. Neo adjuvent chemotherapy
3. Wide/ radical surgery (resection/amputation)
4. Adjuvent chemotherapy
5. Rehabilitation and follow up

Procedure:
1. A multidisciplinary approach in which the surgeons are joint
together with an onchologist, a pathologist, a radiologist
2. After clinical assessment and advanced imaging patient is
admitted to a specialized centre for biopsy
3. Surgeon who will do operation must do the biopsy by
himself
4. Bone sarcomas are broadly divided as follows:
• Stage I All low-grade sarcomas.
• Stage II Histologically high-grade lesions.
• Stage III Sarcomas which have metastasized.

5. Treatment depend upon stage

A. Low grade intracompartmental IA –
i. Wide excision and adjuvant
chemotherapy
B. Stage IIA or IIB - the initiall
presentation Commonly
i. Multi agent neoadjuvant
chemotherapy is given for 8–12 weeks to
reduce size
ii. if tumour is respectable and
there are no skip lesions, a wide resection is
carried out with bone graft or a prosthesis or
custom made implant (limb slavage)
iii. In some cases an amputation
may be more appropriate.
iv. The pathological specimen is
examined to assess the response to
preoperative chemotherapy. If tumour
necrosis is marked (more than 90 per cent),
chemotherapy is continued for another 6–12
months; if the response is poor, a different
chemotherapeutic regime is substituted
C. Stage III
i. small and peripherally situated
Pulmonary metastases
ii. Completely resected with a
wedge of lung tissue.
Therapeutic protocol
1. Neo adjuvant chemotherapy (Preoperative)
 Treatment is started 8–12 weeks
preoperatively
 3 cycles for 3weeks then 3 weeks
gap then operation
 Aim
i. To kill mircrometastasis
ii. To prevent micrometastasis
iii. To reduce the size of primary tumor as well as
metastasis
iv. To reduce the vascularity of tumor & non
operatable tumor become operatable by
downstaging
 Effect is assessed by
i. examining the resected tissue for tumour
necrosis;
ii. greater than 90 per cent necrosis is taken as
a good response.
iii. If there is little or no necrosis, a different
drug may be selected for postoperative treatment.
iv. Maintenance chemotherapy is continued for
another 6–12 months.
Chemotherapy agents are (DMC)
 Doxorubicin
 Methotraxate
 Cisplatin
 cyclophosphomide

2. Surgery
i. Stage IA – (low grade intracompartmental)
ii. Stage IIA – wide excision
iii. Stage IIB – Radical resection
iv. Stage III – Palliative surgery
Wide excision – Removal of tumor, reacting zone &
surrounding margin of normal tissue (tumor free area – 5cm)
Radical resection – Resection of entire compartment in which
the tumor lies is removed enblock without exposing the lesion

3. Adjuvent (postoperative) therapy

i. examining the resected tissue for tumour necrosis;
ii. greater than 90 per cent necrosis is taken as a
good response.
iii. If there is little or no necrosis, a different drug
may be selected for postoperative treatment.
iv. Maintenance chemotherapy is continued for
another 6–12 months.