Osteosarcoma

Osteosarcoma

Prepared by Dr. Sefa Giray BATIBAY

High-grade, malignant, osteoid-producing sarcoma of bone.
Most common primary bone sarcoma.
Arises predominantly in metaphysis of long bones (esp. around the knee).

Epidemiology

• Bimodal age distribution:
  Adolescents (10–20y): Most common (~75%)
  Elderly (>65y): Often secondary to Paget’s, radiation, infarct
• M:F = 1.5:1
• Peak incidence: Distal femur > Proximal tibia > Proximal humerusEpidemiology
• Bimodal age distribution:
  Adolescents (10–20y): Most common (~75%)
  Elderly (>65y): Often secondary to Paget’s, radiation, infarct
• M:F = 1.5:1
• Peak incidence: Distal femur > Proximal tibia > Proximal humerus

 Aetiology & Genetics

• Mostly sporadic
• Associated tumor suppressor mutations:
  RB gene (Retinoblastoma)
  TP53 (Li-Fraumeni syndrome)
• Rare hereditary syndromes:
  Rothmund-Thomson, Bloom, Werner

 Histology

• Malignant mesenchymal spindle cells producing lace-like osteoid
• High N:C ratio, nuclear atypia, mitoses
• Diagnostic criteria:
  Malignant stroma
  Osteoid production

 Subtypes

INTRAMEDULLARY

• Conventional (high-grade)
• Telangiectatic
• Small-cell
• Low-grade variants

SURFACE

• Parosteal (low-grade)
• Periosteal (intermediate-grade)
• Dedifferentiated surface (high-grade)

OTHERS

• Intracortical (rarest)
• Extraskeletal (soft tissue OSA, rare, radiosensitive)

Clinical Features

• Progressive pain + swelling, often attributed to trauma
• Night/rest pain common
• Mass effect, ↓ROM, neurovascular compromise possible
• Median delay to diagnosis: ~4 months

Imaging

X-ray:

• Mixed lytic–blastic lesion
• Sunburst, Codman’s triangle, “Hair-on-end”
• Cortical destruction + soft tissue extension

MRI:

• Assess extent, skip lesions, neurovascular invasion
• Includes entire bone

CT Chest:

• Mandatory for lung metastasis detection

Bone scan / PET-CT:

• Staging, skip lesions

 Staging

• Most are Enneking Stage IIB (high grade, extracompartmental, no mets)
• Stage III if lung/bone mets
• Skip lesions → considered metastasis

 Differential Diagnosis

• Ewing sarcoma (t(11;22), small round blue cells)
• Osteomyelitis (sequestrum, Brodie abscess)
• ABC (vs Telangiectatic OSA)
• Fibrosarcoma, Lymphoma, EG, Leukemia

 Labs

• ↑ ALP & LDH → indicator of high tumor burden
• Histological response post-chemo:
  >90% necrosis = good prognosis

 Biopsy

• Core biopsy by definitive surgeon
• Incorrect biopsy track → ↑amputation risk

 Treatment

1. Neoadjuvant chemotherapy

• 8–12 weeks: MAP regimen (Methotrexate + Doxorubicin + Cisplatin ± Ifosfamide)

2. Wide resection

• Limb-salvage preferred
• Criteria: good chemo response, resectable margins

3. Reconstruction options

• Endoprosthesis
• Allograft/autograft
• Rotationplasty (esp. in children with extensive disease)
• Amputation (if salvage not possible)

4. Adjuvant chemotherapy

• Continue for 6–12 months post-op

 Radiation

• OSA = radioresistant
• Reserved for:
  Extraskeletal OSA
  Palliative settings
  Spine/pelvis with close margins

 Complications

Limb salvage:

• Prosthetic infection (2–10%)
• Aseptic loosening (esp. tibia)
• Nonunion/fracture of grafts
• Local recurrence

Rotationplasty:

• Malrotation
• Vascular compromise
• Cosmesis concerns

Amputation:

• Neuroma, phantom pain, wound healing

 Prognosis

• 5-yr survival (localized):
  ~85% (good chemo response)
  ~65% (general)
• 5-yr survival (metastatic):
  ~20% with pulmonary mets
  Bone mets = poor outcome
• Prognostic factors:
  Response to chemo
  Stage at diagnosis
  ALP/LDH levels
  Tumor size/location
  Surgical margins
  VEGF or MDR expression 

 Clinical Features

• Progressive pain + swelling, often attributed to trauma
• Night/rest pain common
• Mass effect, ↓ROM, neurovascular compromise possible
• Median delay to diagnosis: ~4 months

References:

• Whelan JS, Davis LE. Osteosarcoma: Biology, diagnosis, and treatment strategies.Current Oncology Reports. 2018;20(1):2.
  [DOI: 10.1007/s11912-018-0652-0]
• Isakoff MS, Bielack SS, Meltzer P, Gorlick R.Osteosarcoma: Current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33(27):3029–3035.[DOI: 10.1200/JCO.2014.59.4895]
• Orthopaedic Knowledge Update: Musculoskeletal Tumors 4. Eds: Letson GD, Mankin HJ.American Academy of Orthopaedic Surgeons (AAOS), 2016.
• WHO Classification of Tumours Editorial Board.Soft Tissue and Bone Tumours. WHO Classification of Tumours, 5th Edition, Volume 3.
  International Agency for Research on Cancer (IARC); 2020.
• Peabody TD, Attar S, eds.Orthopaedic Oncology: Primary and Metastatic Tumors of the Skeletal System.Cancer Treatment and Research Series. Springer; [Indexed in PubMed/Medline].

Category	Subtype	Features
Intramedullary	Conventional Osteosarcoma	Heterogeneous histology: may contain cartilaginous, fibrous, giant cell, or small round blue cell components.
	Telangiectatic Osteosarcoma	Resembles aneurysmal bone cyst; blood-filled cavities with scant osteoid lining.
	Small-cell	Overlaps with Ewing sarcoma; small round blue cells producing immature osteoid.
	Fibrous dysplasia-like	High-volume fibrous stroma + immature osteoid.
	Desmoplastic fibroma-like	Low-volume fibrous stroma + immature osteoid.
Surface	Parosteal Osteosarcoma	Low-grade; arises from outer periosteal layer.
	Periosteal Osteosarcoma	Intermediate-grade; from between bone surface and inner periosteum.
	Dedifferentiated surface	High-grade surface variant.
Intracortical	Intracortical Osteosarcoma	Extremely rare; arises within cortical bone.
Extraskeletal	Extraskeletal Osteosarcoma	Soft tissue origin; <5% of all cases; requires wide resection and radiation.