3. Introduction
• Osteosarcoma is the most common primary pediatric bone
malignancy, derived from primitive bone-forming (osteoid producing)
mesenchymal cells.
• It occurs in primary and secondary forms
• 2nd most common primary malignant bone tumor after Multiple
Myeloma
• It accounts for approximately 20% of all primary bone tumors.
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6. Epidemiology
• Incidence- ~5 cases per 1 million people per year
• approximately 2.4% of all pediatric cancers
• usually occurs in children and young adults
• bimodal distribution of occurrence
• males > females
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9. Other etiological factors
Associations with secondary osteosarcoma in patients with
• Paget disease
• exposure to beryllium,
• exposure to alkylating agents
• exposure to ionizing radiation
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10. Other etiological factors
• FBJ virus
• osteochondromatosis,
• enchondromatosis,
• fibrous dysplasia,
• orthopedic prosthetics
• bone infarction and infection.
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11. Skeletal distribution
• Primarily affects the metaphyseal region of long bones
• The most common sites are the distal femur and proximal tibia
• These are the most rapidly growing sites of the body and are at
highest risk for malignant transformation
• other common sites include the proximal humerus, proximal femur,
pelvis, jaw and skull.
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13. Gross Pathology
• Arise from multipotent mesenchymal cells
• Mixture of osteoid, fibrous, cartilaginous, necrotic, hemorrhagic,
cystic areas
• Destruction of cortex
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14. Histology
• Stroma - Malignant connective tissue with anaplastic spindle cells
• Matrix of osteoid/fibrous/cartilagenous tissue
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15. History and Physical Examination
• Pain and Swelling are the usual initial presenting symptoms
• Physical examination:
• A palpable mass may be tender and warm with or without an
overlying pulsation or bruit
• Joint involvement with decreased range of motion
• Local or regional lymphadenopathy (unusual)
• Respiratory findings with metastatic forms
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16. Laboratory Studies
• Full blood count, ESR, CRP.
• LDH (elevated level is associated with poorprognosis)
• ALP (highly osteogenic)
• Liver function tests
• Renal function tests
• Urinalysis
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17. Plain X-ray
• Characteristic osteoblastic and destructive lesion
• sun-burst or hair on end pattern of matrix mineralization
• periosteal reaction (Codman's triangle)
• large soft-tissue mass evidenced by soft-tissue shadow
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20. Magnetic Resonance Imaging
• used to determine:
• soft tissue and neurovascular involvement
• evaluate the extent of the tumor for safe resection level
• presence skip metastases
• if skip metastases are found, this is equivalent to metastatic (stage
III) disease
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24. Radionuclide Bone Scan
• Technetium 99 methylenediphosphonate (Tc99 MDP) bone scan is an
effective and readily available imaging modality for detecting bony
metastasis.
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28. Biopsy
• to confirm the diagnosis
• Types
• Fine needle aspiration
• Core needle biopsy eg use of Jamshidi needle
• Open incisional biopsy
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30. Classification
High-grade intramedullary
Conventional Can be sub-classified depending on histology
• fibroblastic
• chondroblastic
• osteoblastic-like
• giant-cell rich
Telangiectatic Histology is similar in appearance to aneurysmal bone
cyst with blood-filled sinusoids with osteoid production
Small-cell Considered to be a histologic combination of Ewing sarcoma
and osteosarcoma as there is small round blue cells with
immature osteoid production
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33. Classification
High-grade surface histological identical to high
grade/conventional/central variant, varies only in
location (being confined to the surface of the bone)
which is thought to represent dedifferentiated
parosteal osteosarcoma
Intermediate-grade surface Periosteal osteosarcoma
osteosarcoma coming from between surface of bone
and inner layer of periosteum
Low-grade surface Parosteal ostesarcoma
surface osteosarcoma coming from outer layer of
periosteum
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37. Enneking staging system
• Stage IA: Low grade, intracompartmental tumor location, no
metastasis
• Stage IB: Low grade, extracompartmental tumor location, no
metastasis
• Stage IIA: High grade, intracompartmental tumor location, no
metastasis
• Stage IIB: High grade, extracompartmental tumor location, no
metastasis
• Stage III: Any grade, any location, metastasis present
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38. AJCC System for Staging of Primary Bone
Sarcomas (8th Edition)
• Stage IA: Low grade, less than 8 cm tumor size, no spread to regional
lymph nodes, no distant metastasis
• Stage IB: Low grade, greater than 8 cm tumor size or skip lesions,
no spread to regional lymph nodes, no distant metastasis
• Stage IIA: High grade, greater than 8 cm tumor size, no spread to
regional lymph nodes, no distant metastasis
• Stage IIB: High grade, less than 8 cm tumor size, no spread to regional
lymph nodes, no distant metastasi
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39. AJCC System for Staging of Primary Bone
Sarcomas (8th Edition)
• Stage III: High grade, discontinuous tumor involvement/"skip" lesions,
no regional lymph nodes, no distant metastasis
• Stage IVA: Any grade, any size, no regional lymph node spread, lung
metastasis
• Stage IVB: Any grade, any size, regional lymph node spread, lung or
extrapulmonary metastasis
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45. Approach to Management
• Management of osteosarcoma requires a multidisciplinary team
• Following specialties are involved to improve outcomes.
• Orthopaedic Surgeon
• Radiologist
• Oncologist (Medical/ Radiation)
• Pathologist
• Physiotherapist
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47. Surgery
• The main goal of surgery is to safely and completely remove the
tumor.
• Historically – amputation.
• limb-sparing procedures have become the standard, mainly due to
advances in chemotherapy and sophisticated imaging techniques
• Limb salvage procedures now can provide rates of local control and
long-term survival equal to amputation.
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49. Surgery
• If the tumor can be removed safely while retaining a viable extremity,
a limb sparing procedure may be appropriate.
• If major nerves or blood vessels are involved, or if complete tumor
removal results in significant loss of function, amputation may be a
better choice
• Patient’s age, desired level of function, cosmetic preference and long-
term prognosis must also be considered
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50. Amputation
• used to be the standard of care, however, with improved
chemotherapy and surgical techniques, this is typically reserved for
failure of limb salvage
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51. Amputation
Indications
• Grossly displaced pathologic fracture
• Encasement of neurovascular bundle
• Tumor that enlarges during preop chemo and is adjacent to
neurovascular bundle
• Palliative measure in metastatic disease
• If the tumor has caused massive necrosis, fungation, infection, or
vascular compromise
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53. Rotationplasty
• Rotationplasty is a procedure that involves resection of the lower
extremity to the level of the distal femur.
• Resection is followed by a 180-degree rotation of the lower extremity
with subsequent reattachment at the distal femur, essentially
transforming the ankle into a “knee” joint such that the plantar
flexors (soleus and gastrocnemius) get converted to knee extensors.
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55. Limb salvage
• The vast majority of patients (about 85 to 90%) with osteosarcoma
undergo limb salvage.
• Limb salvage involves the removal of a tumor from a limb without the
removal of the entire limb itself.
• This process occurs in two main steps: initial resection and
subsequent reconstruction.
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59. Chemotherapy
• Chemotherapy given preoperatively -Neoadjuvant
• Given postoperatively – Adjuvant
• Given for about 8-12 weeks before definitive procedure
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60. Chemotherapy
• Regression of the primary tumor, making a successful limb salvage
operation easier.
• May decrease the spread of tumor cells at the time of surgery
• Effectively treating micrometastases at the earliest time possible.
• It avoids tumor progression, which may occur during any delay
before surgery.
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61. Chemotherapy
Recommended Neoadjuvant/Adjuvant Chemotherapy Regimens for
Initial-Occurrence
• Cisplatin and doxorubicin
• High-dose methotrexate, cisplatin and doxorubicin
• Doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate
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62. Targeted Therapy
• Recommended Regimens for Relapsed, Refractory or Metastatic
Disease
• Regorafenib
• Ifosfamide (high dose) +/- etoposide
• Sorafenib
• Sorafenib and everolimus
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63. Radiotherapy
• Due to improved results with chemotherapy and surgery combined,
RT is rarely used
• Indications for RT
• Incompletely resected tumors with positive margins
• Unresectable tumors
• Palliation of symptoms.
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64. Complications
• Tumor-Specific Complications eg Pathological Fractures
• Treatment-Related Complications
• Chemotherapy Side Effects eg. Nausea, malaise, alopecia, anemia,
and anorexia etc
• Radiation Side Effects eg nausea, vomiting, dry mouth,pneumonitis,
and fibrosis
• Fracture/Non-Union of Allograft/Autograft
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65. Prognostic Factors
• Age
• Gender
• Extent of the disease
• Grade of the tumor
• Size of the primary lesion
• Skeletal location
• Secondary osteosarcoma
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66. Follow up
• Signs of recurrence, metastasis and treatment related complications
• Physical examination, radiographs of the primary site, serial chest
imaging, bone scans.
• 50 % cases with high grade osteosarcoma have some type of relapse
in 5 months
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67. Follow up
• If recurrence is detected, additional surgery (radical amputation)and
chemotherapy may be warranted.
• 5 year survival rate is 5% - 23%
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68. Conclusion
• Clinician must have a high index of suspicion
• Patients with osteosarcoma should ideally be under the management
of an interprofessional team, including specialists from radiology,
pathology, medical/surgical oncology, and orthopedics
• The patient and the family must be educated about the treatment
options, pain management, and support services.
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70. References
• Apleys system of orthopaedics and fractures
• Robbin and Cotran Pathological basics of disease
• Orthobullets
• The bone school
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Editor's Notes
It occurs in primary (no underlying bone pathology) and secondary forms (underlying pathology which has undergone malignant degeneration/conversion), accounting for approximately 20% of all primary bone tumors
first peek is the second decade of life (10-14 years of age is most common)
the second peak is in patients over 65
seen in those with Paget's disease and those who have received prior radiation.
Race- more common in black/hispanic patients compared to white patients
Osteosarcoma accounts for approximately 2.4% of pediatric cancers, making it the eighth most common childhood malignancy.
Hereditary Retinoblastoma: An autosomal dominant condition caused by germline mutations in the RB1 gene, causes bilateral retinoblastoma at an average presenting age of one year
Li-Fraumeni Syndrome: An autosomal dominant disorder due to mutations in the p53 tumor suppressor gene, has been found in up to 3% of children with osteosarcoma
Rothmund-Thompson Syndrome: An autosomal recessive syndrome due to a mutation in the RECQL4 gene, conveys a predisposition to osteosarcoma as well as a characteristic infantile rash, dysplastic osseous structures, alopecia, premature cataracts, and chronic gastrointestinal distress.
Bloom Syndrome: An autosomal recessive disorder caused by mutations in the BLM gene, a gene responsible for maintaining DNA stability during replication
Werner Syndrome: An autosomal recessive disorder, also known as adult progeria, is characterized by premature aging, bilateral cataracts, osteoporosis, short stature, scleroderma-like skin changes, and a predilection for osteosarcoma. A faulty WRN gene is responsible
Finkel-Biskis-Jenkins (FBJ )
Osteochondromatosis( Reichel syndrome) cartilaginous metaplasia within synovial membrane of the joint
Enchondromatosis-(Ollier disease)-benign cartilaginous tumors, arise in close proximity to growth plate cartilage.
The most common locations include the femur (42%, with 75% of tumors in the distal portion of the bone), the tibia (19%, with 80% of tumors in the proximal portion of the bone), and the humerus (10%, with 90% of tumors in the proximal portion of the bone). Other potential sites include the skull or jaw (8%) and the pelvis (8%)
ALP levels will be high due to the increased osteoblastic activity associated with osteosarcoma. Extremely high levels have been linked to heavy tumor burden and are generally considered a poor prognostic indicator.
It is important to evaluate the levels of the biomarkers later in the treatment process as well, as levels may decrease with success therapy or rise with residual disease or recurrence
Periosteal reaction may appear as the characteristic Codman triangle
Extension of the tumor through the periosteum may result in a so- called “sunburst” or “hair on end” appearance
classic” appearance; cells are spindle-like to polyhedral in shape; nuclei are variable in appearance, and cells undergoing mitosis are readily identifiable. Matrix production by the tumor cells may be osseous (“osteoblastic”), cartilaginous (“chondroblastic”), or fibrous (“fibroblastic”) but a combination of the three often presents
Microscopically it has large blood filled spaces and thin septation. Within the septa there is scanty osteoid production by the pleomorphic malignant cells
5% of osteosarcomas.. Arises from surface, invade medullary cavity in late stages
Tends to encircle bone
Low grade,Slow growing
Large ossified mass in centre
Characterized by bony spicule formation perpendicular to shaft
Strands of osteoid producing spindle cells radiating between lobules of cartilage
The ‘shepherd’s crook’ deformity of the proximal femur
chondrosarcoma -Radiographically these appear as large, intraosseous, osteolytic tumors with a narrow zone of transition and irregular, granular calcifications within the matrix described as ‘honeycomb’ or ‘popcorn
The procedure has been shown to provide surprisingly favorable functionality. However, its unusual appearance has been known to cause psychological distress in some patients
he surgical excision of the mass should also include the biopsy site/tract, with a minimum margin of 2 cm, to avoid recurrence of disease from tumor cells, which may have escaped during tissue sampling.
The decision between carrying out limb salvage or amputation is governed by the expected postoperative limb function, potential for complications, psychological acceptance and oncological outcomes.
Limb salvage is possible for approximately 85% of tumors
In general, this process utilizes a combination of a patient’s own cells, purified intrinsic growth factors, and synthetic, scaffold-like matrix materials to induce autologous tissue regeneration.
