Malignant Bone Tumours

Chondrosarcoma

Definition 

 

Malignant cartilage producing tumour 

 

Epidemiology

 

20% of primary bone tumours

 

3rd most common

- 1 in 500 000

 

Relatively non-aggressive / usually Grade I

 

Average age 40

 

Male > Females

 

Two Distinct Types

 

1.  Primary Chondrosarcoma

 

Arises de novo

 

2.  Secondary Chondrosarcoma (1/4)

 

Chondrosarcoma variant

- arises in existing cartilage lesion

- age > 40

- most common in osteochondromas / enchondromas

- also FD / UBC / Paget's / Radiation

 

A.  Secondary chondrosarcoma in Osteochondroma

 

< 1% chance per lesion 

 

Malignant features

- growth after skeletal maturity

- pain

- calcification in cartilage cap

- disappearance of previous calcification

- cartilage cap > 1-3 cm

- hot on bone scan

- erasure of smooth outline

 

B.  Secondary chondrosarcoma in Enchondroma 

 

Malignant features

- scalloping (endosteal erosion)

- periosteal reaction

- fluffy calcification

- size > 6-10 cm rarely benign

- malignant rare < 20 years

- solitary < Ollier's / Maffucci's

 

C.  Grade 1/2

 

Intra-osseous cartilage forming tumour with worrisome clinical or radiological changes

- i.e. pain at site of previous painless enchondroma

- expansion / large size / endosteal scalloping

 

Problem

- is a diagnostic and management dilemma for radiologists / pathologists / orthopaedic surgeons

 

Management

- biopsy

- can miss malignant areas / sampling errors

- probably best to excise in entirety via curettage to examine all tissue

- covert to resection if frankly malignant

 

Variants

 

1.  Dedifferentiated 

 

Area of low grade with juxtaposed area of anaplastic sarcomatous component

- very aggressive tumour

- prognosis is poor

- few survivors two years after diagnosis

 

2.  Clear Cell 

 

Epiphyseal lesion in young males 

- end of major long bones

- proximal humerus and distal femur

 

Likely malignant chondroblastoma

- destructive low grade

- slow growing

- metastasis very rare

 

Histology

- many cells with abundant clear vacuoles lying between abundant heavily calcified chondroid material

- DDx renal cell ca / clear cell sarcoma / adenoca

 

Treatment

- wide excision

 

The benign appearance and lack of calcification is often misleading

 

3.  Mesenchymal

 

Rare

- young patient

- often extra-skeletal, ribs and jaw

- ill defined osteolytic lesion

- high metastatic potential

 

10 year survival 30%

 

Characteristic biphasic pattern 

- areas of cartilage or chondroid matrix 

- interspersed with areas of small spindle cells similar to Ewing's in a hemangiopericytoma pattern

 

Treatment

- surgery + chemotherapy

 

Location

 

1. Central

 

Within diaphysis of long bone

 

Lytic lesion with punctate or spotty calcification

- can look like bone island

- 3/4 calcification present on plain film

 

Endosteal scalloping is hallmark of chondrosarcoma

- periosteal reaction often minimal

- soft tissue expansion

- in metaphysis may only see subtle periosteal reaction

- expansion with cortical thickening characteristic (20%)

 

Chondrosarcoma Proximal Femur Xray0001Chondrosarcoma Proximal Femur Xray0002

 

2. Peripheral / Juxtacortical

 

Rare

 

Faintly visible sparse calcification in soft tissues

- often behind knee

- radiating spicules at right angles to cortex

- > 2.5cm (OS <1.5cm)

 

Usually no medullary involvement

- cortex rarely affected

- Codman's triangle occasionally

 

3. Soft Tissue

 

Chondrosarcoma Soft Tissue

 

Rare

Treat as soft tissue sarcoma

 

Clinical

 

Pain (80%)

- pain in benign cartilage tumour must be assumed to be malignant

 

Mass

Referred pain

Pathological fracture

Incidental finding

 

Site

 

Pelvis most common

Shoulder / Femur

 

X-ray

 

Worrisome features

- central

- large > 5cm 

- cortical / endosteal scalloping

- cortical break through

- soft tissue mass

- periosteal reaction

 

Pathology

 

Gross

 

Pearly white

- cauliflower-like mass

- surrounded by pseudocapsule

 

Histology

 

Lobules of cartilage

 

Matrix may have

- calcium / necrosis / myxoid degeneration

 

Features that suggest malignancy

- pleomorphism

- hypercellularity

- mitotic figures

- double nuclei in single lacunae

- multinucleated giant cells

 

Can be a great diagnostic challenge for MSK pathologist

- DDx between benign active and low grade (grade 1/2)

- especially difficult between enchondroma and low grade central CS

 

Grading

 

Borderline / Grade 1/2

 

Low-Grade / Grade 1

 

Mild cell atypia and mild hypercellularity

- frequent calcificaiton

- mitoses absent / necrosis rare

- occasional bi / trinucleate cell

 

Medium-Grade / Grade 2

 

More cellular

- 1-2 mitoses / high power field

- less calcification

 

High-Grade / Grade 3

 

Marked atypia & mitotic figures

- densely cellular

- many double nuclei

- no calcification

- obviously anaplastic

- must have chondroid

 

Management

 

Principles

 

Treatment is wide resection

 

Highly resistant to chemotherapy & radiotherapy

- rate of DNA synthesis slow

 

Radiotherapy

- only used if inoperable

- high grade lesions with incomplete margins

 

Exceptions

- mesenchymal -> chemo & radiotherapy

- dedifferentiated -> chemotherapy

 

Surgery

 

Hemipelvectomy Chondrosarcoma

 

Prognosis

 

1.  Grade

 

Low / moderate Grade - 90% 5 year survival

 

High Grade - <10% 5 year survival

 

2.  Site

 

Peripheral - 80% 10 year survival

 

Central - 30% 10 year survival

 

Metastasis

 

Incidence 15%

- 40% preceded by local recurrence

- local recurrence 6x risk for metastasis

 

Grade II:   15 - 40% risk metastasis

Grade III:  75% risk metastasis

 

 

Ewings Tumour

Principles

 

Treatment algorithm similar to OS

 

Overall prognosis similar to OS

- 70% long term survival

 

Definition

 

A malignant neoplasm composed of small round cells of uncertain histogenesis

 

Genetics

 

Recent data suggests it is of neuroepithelial derivation

- ? neuroectodermal cells

- mesenchymal stem cell of neural crest origin

 

Translocation 

- T (11, 22) 

- balanced 

 

Ewing's tumour & PNET have a similar histogenesis

 

Location

 

Central 

- pelvis (12%)

- scapula

- vertebrae

- rib

- sacrum

 

Peripheral 

- femur (20%)

- humerus (11%)

- fibula

 

Epidemiology

 

Usually 2nd decade

- 5-30 years

- peak 10 years

 

M:F 3:2

 

History

 

Usually complain of pain & then swelling

 

± Systemic symptoms

- fever, weight loss, malaise

- poor prognosis

 

Examination

 

Usually large soft tissue mass

 

May have local signs

- tenderness

- erythema & induration

 

Xray 

 

Diffuse permeative destruction

 

Ewings Tumour AcromionEwings Tumour Proximal Femur

 

Extension into soft tissue

 

Periosteal reaction

- codman's triangle

- onion skinning

- sunburst appearance

 

DDx on x-ray

 

Ewing's

Osteomyelitis

EG

 

Blood Tests

 

Elevated ESR & LDH 

- poor prognosis

 

May have anaemia or leucocytosis

 

Lung CT 

 

Pulmonary metastasis (20% GIII)

 

MRI 

 

Shows intramedullary extent 

- extraosseous extent more difficult

- reactive oedema difficult to distinguish from tumour

 

MRI Ewings Sarcoma Proximal FemurMRI Ewings Tumour Proximal Femur

 

Bone Scan

 

Shows occult bone metastases

- 10% have multiple bone involvement at time of presentation

 

Ewings Bone Scan

 

Bone marrow aspirate

 

Important part of staging for Ewing's

 

Staging

 

Usually Grade IIB lesion 

- high grade & extracompartmental

 

20% Grade III

- pulmonary mets

 

In reality all have micrometastasis

 

Bone marrow aspirate and trephine

- at distant site 

- look for marrow spread

 

Histology

 

Sheets of uniform round cells / small round cell tumours

- cells have distinct nuclei with minimal cytoplasm

- indistinct cytoplasmic border

- mitotic activity seldom high

 

Areas of necrosis

- 'geographic necrosis'

- pseudorosettes of cells around central necrosis

 

DDx

 

Use histology, immunohistochemistry, EM and cytogenetics 

- Ewings

- PNET

- lymphoma

- rhabdomyosarcoma

- metastatic neuroblastoma

 

1.  Ewings

 

PAS reaction positive 90%

- stains glycogen and mucin

- other tumours can be positive i.e. neuroblastoma

 

Ewing / PNET

- positive to vimentin / S100 / MIC 2

- MIC 2 specific for neuroectodermal tumours 

 

Cytogenetics

- 11:22 translocation in all  PNET 

 

2.  PNET (Primitive Neuroectodermal Tumour)

 

Variant of Ewing's

 

Composed of

- adult neuroblastoma

- Ewing-like tumour

- Askin tumour - thoracopulmonary PNET

 

Separate group because older age group with worse prognosis

 

3.  Lymphoma of bone 

 

Most important

- older age

- more bone formation

- "common leukocyte antigen" positive

 

4.  Rhabdomyosarcoma

 

Actin / desmin / myoglobin positive

 

EM

- cytoplasmic filaments

- occasional Z bodies

- prominent IC glycogen storage deposits

 

5.  Metastatic neuroblastoma

- PAS positive

- negative to vimentin, MIC 2

 

Other

- small cell OS

- mesenchymal cell chondrosarcoma

- osteomyelitis 

- Eosinophilic Granuloma

 

Management

 

Historically

 

Irradiation only 

- poor results

- survival 25% at 5 years

- local recurrence 35%

- high complication rate (soft tissue damage / pathological fracture / premature closure of physes / 2° sarcoma)

 

Now

 

Chemotherapy is mainstay & primary treatment

- surgery / radiotherapy adjuvant treatment

- significantly more successful

- 60% survival at 5 years

- 40% if metastasis on diagnosis

 

Algorithm

 

1. Neoadjuvent chemotherapy

 

2. Restage

 

3. Surgical resection

- if can get adequate margins

 

4. Chemotherapy

 

5.  Radiotherapy

- if margins inadequate

 

1.  Neoadjuvant Multidrug Chemotherapy

 

Usually dramatically shrinks tumour

- entire soft tissue component can resolve

- period controversial

- principle is to treat to maximum response

 

Pre - chemothearpy

- LFT's / Renal function / Cardiac echo or Thallium scan prior to intensive chemotherapy

- preserve sperm / ovum

 

VAAC Regime

- Vincristine

- Actinomycin

- Adriamycin

- Cisplatin

 

Alternate with

- Iphosphamide

- VP 16 = Etoposide

 

2.  Restage radiographically

 

See response following neoadjuvent chemotherapy

- MRI of affected region

- CT Chest

 

3. Wide Resection ± DXRT of residual tumour

 

Excision best if possible

- amputate if limb salvage not possible

- irradiation if resection not feasible

- resect bone to pre-chemo margin 

- resect ST to post-chemo margin

 

Assess histological response

- > 95% necrosis

 

Surgery improves survival

- removes remaining cancer cells

- removes chemo resistant cells 

 

4. Adjuvant Chemotherapy

 

Continue neoadjuvant regimen

- total chemotherapy is usually 18/12

 

Prognosis

 

1.  Site

- hands and feet better than pelvis and central

 

2.  Size

- > 8-10 cm do worse

- > 100 ml on CT

 

3.  Metastasis at diagnosis

 

4.  Response to chemotherapy

- > 95% necrosis

 

5.  Surgery

- improves survival if resectable

 

Survival

 

No metastasis at diagnosis

- 60% 5 year

 

Metastasis at diagnosis

- 40% 5 year

 

Local recurrence

- 5% local recurrence with surgery

- 25% without

 

Radiotherapy

 

Indications

- incomplete surgical margins

- unresectable

 

If need to use RTX, should use prosthesis rather than allograft

 

Complications

- physeal arrest

- joint contractures

- muscle atrophy

- pathological fracture

 

Secondary malignancy / sarcoma

- increased with young age

- 40x increase if >60 Gy

- strong cumulative risk at 10 years of 35% secondary malignancy

 

 

 

Juxtacortical Osteosarcoma

Epidemiology

 

Uncommon

- 4% OS

 

Females more common 

- similar to GCT

 

NHx

 

Less aggressive locally

- less metastasis

- size / location & duration of symptoms don't correlate with outcome

 

Arise from cortex of bone / periosteum

- parosteal 

- periosteal

- high grade juxtacortical

 

Parosteal Osteosarcoma

 

Epidemiology

 

Comprise most of the 4%

Older (20-40)

Females

 

NHx

 

Lower grade

 

May dedifferentiate (late) into high grade lesion

 

Location

 

Arises from periosteal surface

- in the soft tissues adjacent to the periosteum 

 

Most common in posteromedial distal femur 

- popliteal Fossa

 

Also tibia & humerus

 

Slow indolent growth with eventual invasion of the underlying bone

 

Clinical

 

Painless block to knee flexion

 

X-ray

 

Parosteal Osteosarcoma XrayParosteal Osteosarcoma Xray Lateral

 

May look like osteochondroma

- large lobulated broad-based lesion

- mature bone arising from cortex

- underlying cortex may be thickened

- 25% invade periosteum

- lesion dense with bony pattern

 

"String Sign"

- wraps around bone with intervening periosteum

- gives well-defined radiolucent line

- thin radiolucent line between lesion & cortex

 

CT / DDx from Osteochondroma

 

1. Parosteal OS 

- attached to cortex growing into ST

- normal cortex intact

 

Parosteal Osteosarcoma CT0001Parosteal Osteosarcoma CT0002

 

2. Osteochondroma

- cortex of bone becomes cortex of osteochondroma

- there is modelling of cortex into the tumour

- medullary canal confluent with Exostosis

- posterior femur rare

 

DDx

 

NB Cortical tumours of posterior femur should be considered malignant

 

Osteochondroma

 

Myositis Ossificans

- more mature in periphery

- "like an agg"

- not attached to bone

 

Classic OS

 

Periosteal Chondroma

 

Osteoma

 

Subperiosteal Haematoma

 

MRI

 

Parosteal Osteosarcoma MRI0001Parosteal Osteosarcoma MRI0002

 

Pathology

 

Low grade

 

Regularly arranged bone

- background of spindle cells & fibrous tissue

- may have cartilage cap

- can encircle bone

 

Management

 

Wide Resection

 

Margins

- 7cm proximal & 5cm distally 

- femur: resect posterior capsule & condyles with lesion

 

Parosteal OS Resection0001Parosteal OS Resection0002

 

Prognosis

 

80% cure with surgery alone

 

Periosteal Osteosarcoma

 

Epidemiology

 

Rare +++

15-25

 

Location

 

Diaphysis of major long bones

- typically anterior proximal tibia

- humerus

 

Periosteal Osteosarcoma Anterior Tibia

 

NHx

 

"Peri is a rare bad boy"

- higher grade

 

Pathology

 

AKA High grade juxtacortical chondroblastic OS

- classically shows cartilage +++ 

- c.f. parosteal OS

 

X-ray

 

Punched out lesion

- calcified mass

- in a saucer shaped defect in the cortex

 

MRI

 

Periosteal Osteosarcoma MRI

 

Management

 

Wide resection with neoadjuvant & adjuvant chemotherapy

- DXRT stop local recurrence

 

Periosteal Osteosarcoma Wide Resection0001Periosteal Osteosarcoma Wide Resection0002

Myeloma

Definition

 

Uncontrolled proliferation of single clone of plasma cells

 

Epidemiology

 

Most common malignant tumour of bone

 

Age 50-60

 

2-3 / 100 000

 

Pathology

 

Highly differentiated B lymphocytes

- associated with abnormality of protein synthesis

 

Usually bone marrow of entire skeleton involved

 

Two Forms

 

1.  Multiple Myeloma 95% 

 

2.  Plasmacytoma 5% 

- solitary bone or soft tissue lesion

- usually axial skeleton

- usually disseminates to MM in 5 - 10 years

 

Location

 

Always spine

 

Common in skull, ribs, sternum and pelvis

 

History

 

Bone pain / fatigue / fever / night sweats

 

Laboratory

 

Normocytic normochromic anaemia

 

Other signs bone marrow depression

- i.e. coagulation defects

- leukopenia

- thrombocytopenia

 

Elevated ESR > 100

 

Bence Jones Proteins in urine 50%

 

Serum & Urine Electrophoresis

- monoclonal antibody band

- most sensitive

 

Hypercalcaemia

Chronic Renal Failure

Elevated Serum Urate / Gout

 

Systemic Problems

 

Anaemia

Coagulation defects

Infection 2° immunological deficit

Hypercalcaemia

Amyloidosis 10%

CRF

Gout

 

X-ray

 

1.  Radiographic hallmark is punched out lytic lesions

- axial and appendical skeleton

- widely disseminated / soap bubble appearance

- no sclerotic reaction

 

Multiple Myeloma Pelvis0001Multiple Myeloma Pelvis0002Myeloma Humerus

 

2.  Diffuse osteopenia

- in 15% to 25% of patients, no discrete lysis occurs

- diffuse osteopenia and osteoporosis are the only skeletal manifestations

 

Multiple Myeloma Diffuse Osteopenia

 

3.  Vertebrae Plana

 

Spine Multiple Myeloma

 

4.  Pathological Fracture

 

5.  Pepper pot skull

 

Bone Scan

 

25% negative

- no malignant or reactive bone formation

 

Skeletal Survery

 

Required if negative bone scan

 

Xray

- skull / spine / humerus / femurs / pelvis / chest & ribs

 

Bone Marrow Biopsy

 

Definitive Diagnosis

 

Histology

 

Plasmocytoma Nephron GNU Free Documentation License Version 1.3

 

Sheets of plasma cells

- clock-faced eccentric nuclei

- perinuclear clear area

- increased rER on EM

- no background stroma

 

Cellular atypia not prognostic

 

May see amyloid

 

Management

 

Plasmacytoma 

 

Diagnostic criteria

 

Single osseous lesion confirmed on histology

Bone marrow aspirate from separate site

- < 10% plasmocytosis

No significant BJ in urine

No Ig abnormality in serum or urine

 

Clinical

 

Tend to be younger and have better prognosis

- usually long bone or vertebrae

- in spine commonly present with rapidly progressive paraplegia

- this is more common in plasmacytoma then multiple myeloma

 

NHx

 

70% of plasmacytoma will progress to multiple myeloma

 

Management

- requires biopsy

- resection of lesion if possible

- aggressive DXRT otherwise

 

Prognosis

 

30% cured by surgical en bloc excision and radiotherapy

 

Multiple Myeloma

 

Management

 

Chemotherapy

- corticosteroid

- alkylating agent - Melphalan / Cyclophosphamide

 

Radiotherapy

 

Surgical stabilisation of pathological fracture

 

Orthopedic Management

1. To confirm diagnosis - biopsy isolated lesion

2. To treat impending or actual pathological fracture

3. Rarely to excise solitary lesions

 

Prognosis

 

Multiple myeloma very aggressive with early death

 

 

Osteosarcoma

Definition

 

Highly malignant spindle cell sarcoma of bone in which the malignant cells produce osteoid

- aggressive

- most High grade (II)

- most extracompartmental (IIB)

 

Exception is Juxtacortical (IA)

 

Epidemiology 

 

Most common malignant primary bone tumour excluding myeloma

 

Bimodal peak

 

1.  Second decade / teenagers

- 75%

 

2.  Elderly / 7th decade

- Paget's

 

In fact very rare to see under 13 years

- if looks like OS in this age group then probably Ewing's

 

M > F 3:2

 

Aetiology

 

Li-Fraumeni syndrome

Retinoblastoma - FHx / p53 Defect

Radiotherapy

Paget's disease

 

Classifications

 

Anatomical

 

Classic Central 

- classic high grade

- rare low grade

 

Juxtacortical

- parosteal

- periosteal

 

Extraskeletal

- Jaw

 

Pathological / Lichenstein's

- see below

 

Aetiological 

 

Secondary

- Paget's

- previous radiotherapy

- OM

- Fibrous Dysplasia

- Chondrosarcomatous dedifferentiation

 

Classic Central Osteosarcoma

 

Location

 

Metaphysis of long bones

- distal femur 35%

- proximal tibia 20%

- proximal humerus 10%

 

Osteosarcoma Proximal Tibial Xray0001Osteosarcoma Proximal Tibial Xray0002

 

Can cross into epiphysis / occasionally in diaphysis

 

Presentation

 

Pain

- often activity related

- likely due to microfracture

- most patients relate onset of pain to some minor trauma

- sometimes at night

 

No systemic symptoms

 

Mean symptom duration is 4/12

- 10% metastasis on presentation

- 1% pathological fracture

 

X-ray

 

Usually diagnostic 

 

Osteosarcoma Distal Femur0001Osteosarcoma Distal Femur0002

 

1.  Metaphyseal - involves medullary canal

 

2.  Permeative cortical destruction

 

3.  New bone formation / osteoid

 

4.  Wide / permeative zone of transition / non geographic

 

5.  Codman's Triangle

- triangular periosteal new bone formation

- at proximal and distal cortical margins

- non specific

- reaction to rapid growth

 

6.  Soft tissue component

 

MRI 

 

Osteosarcoma MRI0001Osteosarcoma MRI0002

 

1.  Determines the marrow extent of tumour

- helpful in determining appropriate resection level

- satellite lesions 

- metastasis within reactive zone

 

2.  Identify skip lesions 

- metastasis outside reactive zone

- sagittal and coronal images of the entire bone

 

3.  Soft tissue component

 

Osteosarcoma Proximal Tibial MRI0001Osteosarcoma Proximal Tibial MRI0002

 

4.  Relationship to NV structures

 

5.  Articular involvement

- usually runs along ACL / PCL

 

CT 

 

Complementary to MRI / very useful in the pelvis

 

Bone Scan

 

1.  Resect with 3-4cm margin from bone scan uptake

- resect skip lesions

 

Osteosarcoma Bone Scan

 

2.  Identifies metastatic disease

 

CT Chest / abdomen

 

10% present with pulmonary metastasis

- lungs most common site

- detect > 3 mm

- if resectable then resect lung metastasis via sternotomy

 

Laboratory

 

ALP & LDH

- can be increased 

- worse prognosis 

 

ESR

- May be mild increase

 

Pathology

 

Gross Pathology

 

Starts with intramedullary focus

- bony with areas of focus & haemorrhage

- skip lesions common 5-20% 

- grows up & down medulla

 

Histology

 

Must see malignant spindle cell stroma producing osteoid

- can be difficult to find osteoid

- therefore adequate sampling is essential

 

Osteosarcoma Nephron GNU Free Documentation License Version 1.3Osteosarcoma High Mag Nephron GNU Free Documentation License Version 1.3

 

Pleomorphic spindle cells 

- hyperchromatic nuclei 

- atypical mitotic figures

 

Can mistake fracture callous or periosteal new bone for that produced by malignant cells

 

Low grade central / parosteal OS

- much less cellular

 

Lichenstein Pathological Classification

 

1.  Osteoblastic (50%)

- prominent osteoid 

- delicate network of eosinophilic matrix with both benign and malignant osteoblasts throughout

 

2.  Chondroblastic 

- prominent cartilage

- still have malignant osteoid 

 

3.  Fibroblastic 

- prominent fibrous tissue

- look like fibrosarcoma

 

4. Telangiectatic 

- worst prognosis

- cystic pools of RBC / Giant cells

- may look completely lytic & expansile on Xray

- often with benign giant cells

- can mistake for ABC or GCT

- however see cellular atypia etc amongst stroma

 

5. Giant Cell Rich Osteosarcoma

- older patients

- similar to MFH

- difficult diagnosis

 

6. Small Cell Osteosarcoma

- similar appearance to Ewings

- responds to chemotherapy like PNET

- nests small cells

 

Management 

 

Prognosis

 

Historically

- amputation 

- 1970's 5 year survival 20%

 

Now

- 70% overall survival

- 90% limb sparing surgery 

 

Algorithm

 

1.  Accurate clinical staging

- local (cross sectional imaging - CT / MRI)

- systemic (bone scan & CT chest / abdomen

- biopsy

2.  Neoadjuvant chemotherapy

3.  Restage

- locally and systemic (MRI / CT Chest)

4.  Wide resection 

5.  Post operative chemotherapy +/- radiotherapy if positive margins

 

Chemotherapy

 

Concept

 

Systemic treatment

- treats micrometastasis

- allows limb salvage

 

Rosen in vivo response dictates outcome

 

Outcome best predicted by response as per Rosen

- some OS have P-Glycoproteins pump

- remove chemo from the cell

 

Grade 1 = no cell death

Grade 2 = Partial <90%

Grade 3 = Necrosis >90%

Grade 4 = Complete necrosis

 

Grade 1 & 2 

- < 50% survival

 

Grade 3 & 4 

- > 75% long term survival in OS and MFH

 

Regimen

 

Neoadjuvant & Adjuvant

 

2 cycles pre-operative MACI

- MTX

- Adriamycin (Doxorubicin)

- Cisplatin

- Ifosphamide

 

Surgery

 

Timing

- usually 3/12 after diagnosis

- usually 2/52 after end neoadjuvant chemotherapy

- post chemotherapy tumour is smaller & tends to have a "rind" that makes resection much easier

 

Goal

- resection with wide margin

- 7cm proximally, 5cm distally

 

Options

 

Amputatation

Limb Salvage Surgery

 

Limb Salvage Surgery

 

80% patients can have limb salvage

 

Contraindications / PIN LEG

 

1. Pathological fracture

2. Infection

3. N/V involvement 

4. Immature skeletal age if LLD >6-8cm

5. Extensive muscle involvement

6. Poor biopsy (instead of Good)

 

Technique

 

1. Resection of tumour & biopsy tract

- major N/V bundle must be free of tumour

- wide resection of affected bone 

- normal muscle cuff in all planes

- biopsy tract removed en bloc

- 5cm margin on MRI

- adjacent joint and capsule should be resected

- extra-articular resection preferred

- articular resection mandatory if effusion present

- use tourniquet --> if site contaminated at histology allows amputation to be performed above tourniquet level

- motor reconstruction by local transfer

 

2. Skeletal reconstruction 

- usually 15-20 cm defect

- endoprothesis / arthrodesis / allograft

 

Osteosarcoma Distal Femur Tumour ProsthesisOsteosarcoma Distal Femur Tumour Prosthesis0001

 

Osteosarcoma Proximal Tibial Resection0001Osteosarcoma Proximal Tibial Resection0002

 

3. Local soft tissue and muscle transfers

- adequate soft tissue cover mandatory

 

 

Local recurrence post OT 

 

Incidence 12%

- poor outcome

- DXRT to prevent local recurrence if +ve margin

 

Can still treat with an attempt at cure

- resectable disease =< 15 pulmonary metastasis + extremity tumour

- treatment is along similar lines

- neoadjuvent chemo

- tumour resection / amputation + median sternotomy and resection of mets

- aim is to relieve tumour burden

- if unresectable then chemotherapy is more appropriate

 

Prognosis

 

Single most predictive factor is the presence or absence of detectable metastasis at presentation

 

Survival

 

IIB 60% 5 year

III  50% 5 year

 

Significant improvement recently

- improved surgical resection

- early resection of lung metastasis

- improved adjuvant chemotherapy

 

Metastasis - 10 - 20% 5 year

 

Resectable pulmonary metastasis post treatment

- 20 - 40% 5 year 

 

CT Chest Solitary Metastasis

 

Local recurrence

- 5 - 10 % 5 year

 

Basic Principles

 

If survive 2 years probably will survive

- no difference in survival between amputation & limb salvage

- long-term survivors 7% risk of developing second tumour due to treatment

 

Poor Prognostic Signs

 

Age < 10 years

Proximal humerus / central lesion

Poor response to chemotherapy

Tumour size > 15cm

Symptoms < 6/12 = aggressive

Pathological fracture

NV involvement

Pelvis much worse than femur which is worse than tibia

Telangiectatic worst

Secondary OS