Tumors and tumor-like lesions of the bone

1. Bone-Forming Tumors

A) Osteoma (Benign)

• Benign; developmental abnormalities or reactive growths.
• Most common location: surface of facial bones.
• Solitary; slowly growing hard exophytic mass.
• Multiple osteomas → Gardner syndrome = FAP + retroperitoneal fibromatosis + osteomas.
• Non-invasive; no malignant transformation → cosmetic problems only.

B) Osteoid Osteoma (Benign)

• Benign neoplasm; typically < 25 yr.
• Gross: well-circumscribed; sclerotic bone rim around central osteoid (“nidus”).
• Histology: anastomosing bony trabeculae with variable mineralization, surrounded by osteoblasts; loose vascular stroma + giant cells.
• Symptoms:
  • Localized pain, worse at night.
  • Due to PGE2 production.
  • Pain relieved by aspirin (key clinical clue).
• Tx: local excision; recurs if incomplete.
• Rarely transforms to malignancy unless irradiated.

C) Osteoblastoma (Benign)

• Similar to osteoid osteoma but:
  • Larger (> 2 cm).
  • Tends to occur in vertebrae.
  • Pain is difficult to localize, NOT relieved by aspirin.

D) Osteosarcoma (Malignant)

• Malignant bone tumor producing osteoid directly from tumor cells.
• Bimodal age:
  • Early peak < 20 yr → RB gene mutation (inherited retinoblastoma survivors at risk).
  • Late peak > 40 yr → Paget disease, prior radiation.
• Pathogenesis: mutations in cell cycle regulators (p53, RB, cyclins, kinase inhibitors).

Morphology

• Most arise in metaphysis of long bones of the extremities (around the knee: distal femur, proximal tibia).
• Gross: gray-white tumor infiltrating cortex → soft tissue mass.
• Histology: high-grade spindle cell tumor producing osteoid matrix (pink lacy matrix between malignant cells).
• X-ray:
  • Large destructive, lytic or blastic mass with infiltrating margins.
  • Codman’s triangle: triangular periosteal elevation — tumor grows so fast that it lifts the periosteum off the bone.
  • Sunburst pattern of periosteal reaction.

Clinical features

• Bone pain + swelling.
• Pathologic fracture (tumor produces unmineralized bone).
• Hematogenous spread to lungs.
• Tx: chemotherapy + surgical excision; metastatic nodule excision may prolong survival.

2. Cartilage-Forming Tumors

Produce hyaline or myxoid cartilage.

A) Osteochondroma (Benign)

• Benign cartilage-covered outgrowth connected to skeleton by bony stalk.
• Solitary (adults) or multiple (childhood).
• EXT gene mutation (encodes cartilage component).
• Arises in metaphysis of long tubular bones (especially around the knee).
• Hereditary multiple osteochondromas → ↑ malignant transformation → chondrosarcoma.

B) Chondroma (Benign)

• Benign hyaline cartilage tumor.
• Usually in small bones of hands + feet.
• Types:
  • Enchondroma: within medulla.
  • Juxtacortical chondroma: on bone surface.
• Syndromes:
  • Maffucci syndrome: multiple enchondromas + soft tissue hemangiomas.
  • Ollier disease: non-hereditary multiple enchondromas of long + flat bones.
• Tx: excision; may recur if incomplete.

C) Chondrosarcoma (Malignant)

• Malignant cartilage-forming tumor (may arise from osteochondroma).
• 30–60 yr, males.
• Sites: pelvis, ribs, knee — painful enlarging masses.
• Gross: pearly-white or light blue, focal calcification.
• Grade 1: rarely metastasizes; Grade 3: usually hematogenous mets to lungs + skeleton.
• Low-grade → thickens cortex; high-grade → destroys surrounding bone.

3. Miscellaneous Bone Tumors

A) Giant Cell Tumor of Bone (Osteoclastoma)

• Intermediate, locally aggressive neoplasm.
• Sheets of neoplastic mononuclear cells interspersed with large osteoclast-like giant cells.
• Young adults; arises in epiphysis of long bones around the knee.
• Gross: red-brown, cystic degeneration, hemorrhage, necrosis.
• X-ray: expanding, eccentric, lytic areas (“soap-bubble” appearance); well-defined margins.
• Sx: pain, limited joint movement, swelling, pathologic fracture.
• Lung metastasis possible.

B) Ewing Sarcoma / PNET

• Primary malignant tumor of bone + soft tissue.
• From neuroectoderm; mainly children.
• PNET shows neural differentiation; Ewing sarcoma is undifferentiated.

Morphology

• Arise in medullary cavity → invade cortex + periosteum → soft tissue mass.
• Histology: sheets of small, round, uniform cells in irregular lobules with fibrous strands.
• Homer-Wright pseudorosettes present.

Pathogenesis

• t(11;22) translocation → EWS-FLI1 fusion gene (EWS gene + ETS family transcription factor) → constitutively active TF → cell proliferation.

Clinical features

• Sites: pelvis, ribs, vertebrae, femur, tibia (diaphysis).
• Pain, fever, anemia → may mimic osteomyelitis.
• X-ray: destructive lytic tumor + reactive periosteal bone — “onion-skin” appearance.
• Tx: chemotherapy + surgical excision; 5-yr survival ~75 %.

4. Metastatic Tumors

• #1 malignant tumor of bone overall.
• Usually osteolytic / punched-out lesions.
• Adult primaries: prostate, breast, kidney, lung, thyroid (mnemonic: “BLT-KP”).
  • Prostate → osteoblastic; others → osteolytic.
• Child primaries: neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma.

5. Summary Table

Tumor	B/M	Age	Location	Key feature
Osteoma	B	Adult	Facial bones	Gardner syndrome (multiple)
Osteoid osteoma	B	< 25	Long bones, cortex	Night pain relieved by aspirin; nidus < 2 cm
Osteoblastoma	B	Young	Vertebrae	Pain not relieved by aspirin; > 2 cm
Osteosarcoma	M	< 20 / > 40	Metaphysis around knee	Codman triangle + sunburst; RB/Paget/radiation; lung mets
Osteochondroma	B	Adolescent	Metaphysis long bones	Most common benign bone tumor; cartilage-capped stalk; EXT
Enchondroma	B	Adult	Hands/feet medulla	Maffucci + Ollier syndromes
Chondrosarcoma	M	30–60	Pelvis, ribs, knee	Hyaline cartilage; pearly white; lung mets
Giant cell tumor	Locally aggressive	Young adult	Epiphysis around knee	Soap-bubble lytic; osteoclast-like giant cells
Ewing sarcoma	M	Children	Diaphysis (pelvis, ribs, long bones)	Onion-skin periosteum; t(11;22) EWS-FLI1; Homer-Wright; small round blue cells
Metastatic	M	Adult	Any	#1 malignant bone tumor; prostate = blastic, others lytic

💡 High-yield: Osteoid osteoma = young, cortex, night pain relieved by aspirin (PGE2). Osteoblastoma = vertebrae, aspirin doesn’t help. Osteosarcoma = bimodal (RB/p53; Paget/radiation), metaphysis around knee, Codman triangle + sunburst, lung mets. Osteochondroma = #1 benign; cartilage-capped stalk, EXT. Enchondroma = small bones of hands/feet medulla; Maffucci (+ hemangiomas), Ollier. Chondrosarcoma = older adults, pelvis/ribs/knee. Giant cell tumor = epiphysis around knee, “soap-bubble” lytic, osteoclast-like giant cells. Ewing sarcoma = kids, diaphysis, t(11;22) EWS-FLI1, “onion-skin” periosteum, small round blue cells + Homer-Wright. Metastatic = #1 malignant bone tumor; prostate = blastic.