Osteosarcoma

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].

Xray and Mri of the proximal humerus bone tumor

Biopsy fluoroscopy image

Surgery plan drawings

Xray of the resected humerus

Pathologic specimen

Osteosarcoma pathology

Postoperative total shoulder tumor prosthesis