Bones

• Primary bone tumors are rare

  
• Bone sarcomas are lethal in 50% of cases
• Treatment for bone tumors

  Optimize survival while maintaining function
• Majority of cases develop at 1st decade of life and involve the long bones
• Diagnostic clues for bone tumors


  • Age groups and predilection for particular anatomic size

  
• Benign tumors


  Usually incidental findings but may have pain or a slow growing mass

  
• Pathologic fractures


  Sometimes the first hint of malignancy
• Radiography and biopsy required for diagnosis
• Classification is commonly based on the normal cell or matrix produced
• If no counterparts, lesions are grouped based on clinicopathologic features
• Benign tumors are more common than malignant tumors and occur within first 3 decades of life
• Most common primary bone cancers

  • Osteosarcoma
  • Chondrosarcoma
  • Ewing sarcoma

  
• Insults that induce chronic injury and inflammation increase the risk of bone neoplasia due to possible gain of oncogenic mutations
• Bone-forming tumors


  • Osteoid osteoma
  • Osteoblastoma
  • Osteosarcoma

  
• Cartilage-forming tumors


  • Osteochondroma
  • Chondroma
  • Chondrosarcoma

  
• Tumors of Unknown Origin


  • Ewing Sarcoma
  • Giant cell tumor
  • Aneurysmal bone cyst

  
• Lesions simulating primary neoplasm

  • Fibrous cortical defect
  • Non-ossifying fibroma
  • Fibrous dysplasia

  
• Osteoid osteoma and Osteoblastoma


  Benign bone producing tumors that have identical histologic features but differ in size, sites of origin and symptoms

  
• Osteoid osteoma


  • Less than 2 cm in diameter, young men; teens to 20s, predilection: appendicular skeleton usually femur or tibia, arises from the cortex
• Osteoid osteoma signs and symptoms


  Severe nocturnal pain relieved by aspirin and other NSAIDs due to prostaglandin E2 produced by proliferating osteoblasts
• Osteoblastoma


  Larger than 2 cm in diameter, involves the posterior spine, pain is unresponsive to aspirin, tumor does not induce marked bony reaction

  
• Osteosarcoma


  Malignant tumor in which cancer cells produce osteoid matrix or mineralized bone

  
• Osteosarcoma is the most common primary bone tumor, accounting for 20% of all bone cancers

  
• Osteosarcoma


  • Bimodal distribution: 75% younger than 20 years old, smaller peak in older adults, M>F (1.6:1), arises from the metaphyseal region of the long bones

  
• Osteosarcoma presentation


  Presents as painful, progressively enlarging masses, sudden fracture of bone as first symptom
• Osteosarcoma radiographic findings


  • Large destructive mixed lytic and blastic mass with infiltrative margins, tumor breaks the cortex and lifts the periosteum producing reactive periosteal bone formation, Codman triangle

  
• Osteosarcoma pathogenesis


  70% of tumors have acquired genetic abnormalities, RB, TP53, INK4a, MDM2 and CDK4

  
• Osteosarcoma morphology


  • Bulky tumors that are gritty, gray-white, contains areas of hemorrhage and cystic degeneration, destroys the surrounding cortices and produce soft tissue masses, can penetrate the epiphyseal plate, tumor cells vary in size and shape, large hyperchromatic nuclei, bizarre tumor giant cells and bizarre mitosis

  
• Osteosarcoma treatment


  Multimodality approach, neoadjuvant therapy may be given if there is an occult metastasis at the time of diagnosis, but the main treatment is surgery
• Osteosarcoma prognosis

  1. year survival at 60-70% if without overt metastasis, prognosis of metastatic, recurrent disease is poor (<20% in 5 years), metastatic site: lungs (10-20% of affected individuals) followed by brain and other bones
• Osteochondroma

  A benign cartilage-capped tumor attached to underlying skeleton by a bony stalk, most common benign tumor

  
• Osteochondroma

  • 85% are solitary, usually diagnosed in late adolescence or early adulthood, multiple hereditary exostosis syndrome (15% of cases), M > F; 3:1, develop only in bones of endochondral origin and arise form the metaphysis near the growth plate of long tubular bones

  
• Osteochondroma pathogenesis


  Hereditary exostoses: loss-of-function mutation in EXT1 or EXT2 gene, reduced expression in EXT1 or EXT2 gene, EXT1 and EXT2 encode enzymes that synthesize heparan sulfate glycosaminoglycans
• Osteochondroma morphology


  • Sessile or pedunculated; 1-20 cm in size, cap composed of benign hyaline cartilage varying in thickness covered peripherally by perichondrium, cartilage looks like disorganized growth plate with endochondral ossification (new bone at inner portion)

  
• Osteochondroma clinical features


  Stops growing at the time of growth plate closure, symptomatic tumors cured by simple excision

  
• Chondroma


  Benign tumors of hyaline cartilage in bones of endochondral origin, can arise within the medullary cavity (enchondroma) or on the surface of bone (juxtacortical chondroma)

  
• Chondroma


  • Most common of the intraosseous cartilage tumors and diagnosed in ages 20 to 50 years of age, radiography: circumscribed lucencies with central irregular calcifications, sclerotic rim and intact cortex

  
• Nonhereditary disorder with multiple enchondroma

  Ollier disease and Maffuci syndrome
• Chondroma pathogenesis


  Heterozygous mutation in IDH1 and IDH2 genes, enchondroma syndrome: mosaic
• Chondroma morphology


  • Well circumscribed and usually < 3 cm, gray-blue and translucent, well-circumscribed nodules of hyaline cartilage: benign chondrocytes, peripheral portion: endochondral ossification, central area calcifies