STEPTRACKERMUSCULOSKELETAL + ONCOLOGY | PATHOLOGY + GENETICS | HIGH-YIELD REVIEW

Malignant Bone Tumors

Metastases outnumber all primary bone cancers; among primaries, age and location pick osteosarcoma, Ewing or chondrosarcoma.

FOCUS ON
Metastases are the most common malignant bone tumors (breast, prostate, lung, kidney, thyroid). Osteosarcoma: teens, metaphysis around the knee, osteoid-making cells, Codman triangle/sunburst; RB1, TP53, Paget. Ewing: boys, diaphysis, onion-skin, t(11;22), CD99. Chondrosarcoma: older adults, pelvis and shoulder, chemo-resistant.
TUMOR
ORIGIN · GENETICS
FEATURES
CLUE
Osteosarcoma
most common primary malignant
Malignant cells making osteoid; RB1 (hereditary retinoblastoma), TP53 (Li-Fraumeni)
Bimodal: adolescents and older adults; metaphysis of distal femur / proximal tibia; pain, swelling, pathologic fracture
↑ ALP · lung metastases
Osteosarcoma — imaging & risk
Periosteum lifted by tumor
Codman triangle, "sunburst" spiculation; older adults: Paget disease, prior radiation, bone infarcts
Neoadjuvant chemo + limb-sparing surgery
Ewing sarcoma
Neuroectodermal small round blue cell tumor; t(11;22) EWSR1-FLI1
Boys < 15; diaphysis of long bones, pelvis; "onion-skin" periosteal reaction
CD99 ⁺ · very chemosensitive
Ewing — presentation
Systemic inflammatory signs
Fever, ↑ ESR, leukocytosis, local pain and swelling
Mimics osteomyelitis
Chondrosarcoma
Malignant hyaline cartilage; IDH1/2; may arise from enchondroma or osteochondroma
Adults 40–60; axial skeleton — pelvis, proximal femur, shoulder girdle; expansile lesion with ring calcifications
Resistant to chemo/radiation → surgery
Chordoma
Notochord remnant; brachyury ⁺
Sacrum and clivus; vacuolated "physaliphorous" cells
Midline axial tumor in an adult
Bone metastases
most common malignant
Hematogenous spread to red marrow (spine, pelvis, ribs, proximal long bones)
Bone pain, pathologic fractures, cord compression, hypercalcemia
Breast, prostate, lung, kidney, thyroid
Lytic vs blastic metastases
Tumor signals tip remodeling: PTHrP, RANKL (lytic) · endothelin, Wnt (blastic)
Lytic: lung, kidney, thyroid, myeloma · blastic: prostate, small cell lung · mixed: breast
Blastic → ↑ ALP
Multiple myeloma bone disease
Plasma cells secrete RANKL, IL-6, DKK1 (blocks osteoblasts)
Punched-out lytic lesions (skull, spine), hypercalcemia, fractures
Bone scan often negative (no osteoblast activity)
Spinal cord compression
Vertebral metastasis invades epidural space
Back pain (worse lying), then weakness, sensory level, bladder dysfunction
Emergency: steroids + MRI + radiation/surgery

Mechanism — the vicious cycle of bone metastasis

Tumor cell in marrow
→
PTHrP
→
Osteoblasts ↑ RANKL
→
Osteoclasts resorb
→
Released TGF-β, IGFFeed tumor growth

Bisphosphonates and denosumab interrupt the cycle and reduce fractures and hypercalcemia.

Primary bone cancers compared

FEATURE
OSTEOSARCOMA
EWING
CHONDROSARCOMA
Age
10–20 (and elderly)
< 15
40–60
Site
Metaphysis, knee
Diaphysis, pelvis
Pelvis, shoulder
X-ray
Codman, sunburst
Onion-skin
Ring calcification
Histology
Osteoid
Small round blue cells
Malignant cartilage
Gene
RB1, TP53
t(11;22)
IDH1/2
Chemo
Responsive
Very responsive
Resistant

How it's tested

COMMON CONFUSIONEwing sarcoma and osteomyelitis both cause fever, bone pain and high ESR in a child. Onion-skin layering on the diaphysis and small round blue cells point to Ewing.
THE TRAPA solitary bone lesion in an older adult is a metastasis or myeloma until proven otherwise — not a primary bone tumor.
YOUR APPROACHAge → bone region (metaphysis, diaphysis, axial) → periosteal pattern → matrix (osteoid, cartilage, none) → gene/stain → metastasis pattern.

If you see… think…

15-year-old with knee pain, sunburst and Codman triangle → osteosarcoma
Retinoblastoma survivor with a femur tumor → osteosarcoma (RB1)
Paget disease patient with a new painful mass → secondary osteosarcoma
10-year-old boy, femoral diaphysis, onion-skin, fever → Ewing sarcoma
Small round blue cells, CD99⁺, t(11;22) → Ewing sarcoma
55-year-old with expanding pelvic cartilage tumor → chondrosarcoma
Sacral mass with bubbly vacuolated cells → chordoma
Older man with sclerotic spine lesions and ↑ PSA → prostate metastases
Punched-out skull lesions, hypercalcemia, anemia → multiple myeloma
Cancer patient with back pain and new leg weakness → cord compression — steroids, MRI