Conventional Osteosarcoma


Osteosarcoma distal femurOS femur 2OS MRI Femur





Malignant mesenchymal cells producing osteoid




Most common malignant primary bone tumour excluding myeloma


Bimodal peak

1.  Second decade / teenagers - 75%

2.  Elderly / 7th decade - Paget's


Male:Female 3:2




Li-Fraumeni syndrome

Retinoblastoma - FHx / p53 Defect



- Paget's / Radiotherapy / Osteomyelitis / Fibrous Dysplasia

- Chondrosarcomatous dedifferentiation


World Health Organization Classification 2020


Osteosarcoma, not otherwise specified (NOS)

i) Conventional (80%)

- high grade, intramedullary

- osteoblastic / chondroblastic / fibroblastic cell types

- all three types produce osteoid


ii) Telangiectatic (4%)

- blood filled cavities with high grade sarcomatous cells

- can be mistaken for ABC's


iii) Small Cell (1-2%)

- similar to Ewing's

- differentiated by osteoid production


Low Grade Central Osteosarcoma (LGCOS)

- 1-2%

- affects 3rd - 4th decade

- better prognosis



i) Parosteal (4-6%)

- low grade OS arising from periosteum

- typically posterior distal femur


ii) Periosteal

- less common

- forms as a periosteal reaction


iii) High grade surface

- behaves similar to conventional


Conventional Osteosarcoma





- often activity related likely due to microfracture

- most patients relate onset of pain to some minor trauma

- sometimes at night


No systemic symptoms




Typically metaphysis of long bones

- distal femur 35%

- proximal tibia 20%

- proximal humerus 10%


Can be diaphysis / axial skeleton



- new bone formation / osteoid

- permeative cortical destruction

- wide zone of transition

- periosteal reaction

- soft tissue mass


OS femur 1OS femur 2


OS femur 1OS femur 2

Osteosarcoma of the distal femur


Osteosarcoma tibiaOsteosarcoma tibia 1Osteosarcoma tibia 2

Osteosarcomas of the proximal tibia


Osteosarcoma humerusOsteosarcoma fibula

Osteosarcoma of the humerus                                 Osteosarcoma of the fibula


Codman's Triangle

- triangular periosteal new bone formation

- at proximal and distal cortical margins

- reaction to rapid growth


Codman's triangle 1Codmans triangle 2

Codman's triangle in osteosarcoma distal femur




OS femur 1MRI OS FemurMRI OS Femur 2MRI OS Femur 3



i) Soft tissue component

ii) Involvement of neurovascular bundle

iii) Marrow extent of tumour

- helpful in determining appropriate resection level

- satellite lesions - metastasis within reactive zone

iv) Identify skip lesions 

- metastasis outside reactive zone

- sagittal and coronal images of the entire bone

v) Joint involvement


Osteosarcoma Proximal Tibial MRI0001Osteosarcoma Proximal Tibial MRI0002


OS humerus 1Os humerus 2OS humerus 3




Complementary to MRI / very useful in the pelvis


Bone Scan


1.  Identify margins for resection / identify skip lesions


OS bone scanOS femur bone scan


2.  Identify metastatic disease


OS bone scan

Bone scan with isolated disease


Bone scan metsBone scan mets

Bone scan metastasis


CT Chest / abdomen


CT Chest Solitary MetastasisCT chest mets

Pulmonary metastasis





- incisional biopsy

- image guided fine needle aspirate

- image guided core needle biopsy




Dirks et al World J Surg Oncol 2023

- incisional biopsy of 332 malignant musculoskeletal tumours

- sensitivity 100%, specificity 97.6%


Tsukushi et al Arch Orthop Trauma Surg 2010

- CT guided needle biopsy in 207 patients with musculoskeletal lesions

- diagnostic accuracy 90%


Traina et al JBJS Am 2015

- systematic review of 21 articles

- accuracy incisional biopsy > core needle > fine needle

- increased risk of contamination with incisional biopsy




Must see malignant spindle cell stroma producing osteoid


Pleomorphic spindle cells 

- hyperchromatic nuclei 

- atypical mitotic figures



- can be difficult to find

- adequate sampling essential


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




Enneking / Musculosketal tumour society


Stage I:  Low grade

Stage II: High grade

Stage III: Metastasis

A: intra-compartmental

B: Extra-compartmental


Most osteosarcomas are stage IIB






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




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




Localised disease

Response to chemotherapy

Pathological fracture


O'Kane et al Clin Sarcoma Res 2015

- 81 patients with localized disease

- overall survival 70% 7 years

- patients <40 74% 5 year survival

- patients <40 42% 5 year suvival




Preoperative chemotherapy


Four chemotherapy agents

- methotrexate with leucovorin rescue, doxorubicin (AKA adriamycin), cisplatin, and ifosfamide.


Rosen in vivo response dictates outcome

Grade 1: No cell death

Grade 2: Partial <90%

Grade 3: Necrosis >90%

Grade 4: Complete necrosis


O'Kane et al Clin Sarcoma Res 2015

- 81 patients with localized disease

- overall survival 70% 7 years

- >90% necrosis, survival 82% 5 year

- < 90% necrosis, survival 68% 5 year


Tsuda et al Bone Joint J 2020

- 232 patient < 40 years with localized disease

- treated with MAP (methotrexate, adriamycin, cisplatin)

- overall survival 74% 5 years

- chemotherapy induced necrosis associated with survival

- 72% necrosis cut off for optimal 5 year survival in this study


Postoperative chemotherapy


Imran et al JBJS Am 2009

- 703 patients with osteosarcoma

- investigated timing of resumption of chemotherapy post surgery and survival

- overall survival poorer for those with chemotherapy commenced > 21 days post surgery







Limb Salvage Surgery


Mei et al Arch Orthop Trauma Surg 2014

- meta-analysis of 6 studies comparing limb salvage to amputation for osteosarcoma

- similar functional outcomes and quality of life in both groups




Usually 2 weeks after end neoadjuvant chemotherapy




Bony resection with wide margins

- 5 - 7 cm


Limb Salvage Surgery


80% patients can have limb salvage


Contraindications / PIN LEG


1. Pathological fracture

2. Infection

3. Neurovascular involvement 

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

5. Extensive muscle involvement

6. Poor biopsy (instead of well performed biopsy)




Vumedi resection distal femur osteosarcoma and insertion megaprosthesis


Vumedi resection proximal tibia osteosarcoma and insertion megaprosthesis


1.  Resection of tumor and biopsy tract

2.  Skeletal reconstruction

3.  Soft tissue cover


Resection of tumor & biopsy tract


Major neurovascular bundle must be free of tumor

- wide resection of affected bone 

- normal muscle cuff in all planes

- biopsy tract removed en bloc

- 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


Skeletal reconstruction


Options for 15 - 20 cm defect

- megaprothesis

- massive allografts




Modular, silver coated titanium megaprosthesis




Gosheger et al J Arthroplasty 2008

- 197 patients treated with megaprosthesis

- infection rate cobalt chrome 31%

- infection rate titanium 14%


Fiore et al Eur J Orthop Traumatol 2021

- meta-analysis of 19 studies using megaprosthesis

- infection rate with silver coating 9% versus 11% without

- infection rate with revisions with silver coating 14% versus 29% without


Osteosarcoma Distal Femur Tumour ProsthesisOsteosarcoma Distal Femur Tumour Prosthesis0001

Post distal femoral osteosarcoma resection


Femoral megaprosthesis 2Femoral megaprosthesis 1

Post distal femoral osteosarcoma resection


Osteosarcoma Proximal Tibial Resection0001Osteosarcoma Proximal Tibial Resection0002

Post proximal tibial osteosarcoma resection


Humerus Megaprosthesis 1Humerus megaprosthesis 2




Zhang et al Int Orthop 2018

- cemented megaprosthesis for high grade osteosarcoma around the knee

- 108 patients with average age 25

- 5 year prosthesis survival 78%

- 8 year prosthesis survival 55%


Sadek et al Ann Surg Oncol 2023

- modular endoprosthesis for osteosarcoma of the distal femur

- 82 patients

- 5 year prosthesis survival 68%

- 10 year prosthesis survival 52%

- aseptic loosening commonest complication 19.5%

- deep infection 15.9%


Ebeid et al Ann Surg Oncol 2023

- modular endoprosthesis for osteosarcoma of the proximal tibia

- 55 patients

- 5 year prosthesis survival 82%

- 10 year prosthesis survival 62%

- aseptic loosening commonest complication 14.5%

- deep infection 14.5%

- periprosthetic fractures 16%


Loos megaprosthesis 1Loose megaprosthesis 2

Megaprosthesis aseptic loosening


Massive osteochondral allografts


Bus et al Bone Joint J 2017

- 20 year follow up of 26 patients treated with massive osteochondral allograft

- 53% graft failure

- recommended against their use


Local soft tissue and muscle transfers



Pathological fracture and osteosarcoma


OS path # 1OS path # 2




Poorer prognosis likely related to higher incidence distant disease

Limb salvage not precluded

Adults have poorer prognosis than pediatric population




Salunke et al Bone Joint J 2014

- systematic review and meta-analysis

- pathological fracture 303/1713 (18%)

- local recurrence with fracture 14% versus without fracture 11%

- five year survival with fracture 49% versus without fracture 67%

- no difference between amputation and limb salvage


Zhong et al Am J Transl Research

- systematic review

- pathological fracture associated with poorer prognosis

- likely related to increased association of distant metastasis

- no significant difference between amputation and limb salvage


Kelley et al J Clin Oncol 2020

- cohort of 2,200 patients with OS

- incidence pathological fracture 11%

- no difference in overall survival in pediatric population

- 5 year survival adults with fracture 46% versus without 69%




Mettman et al, Cancer Med 2023

- Retrospective RV of 219 osteosarcoma patients who relapsed with a single pulmonary nodule

- 94.9% achieved successful resection of nodule

- 5y survival post complete resection was 51%, compared to 0% if incomplete

- resection technique (thoracotomy vs thoroscopy), chemo, radiation made no difference