General
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• Most common primary bone tumor after myeloma
• Definition: malignant bone tumor that produces osteoid directly from tumor cells and unconnected with cartilage, regardless of the amount of neoplastic cartilage or fibrous tissue present elsewhere
• 60% male; usually ages 10-25 years or ages 40+ with other diseases (see below); rare before age 5
• Associated with Paget disease after age 40 years (see below), post-radiation exposure (see below), Thorotrast administration, chemotherapy in children, fibrous dysplasia, osteochondromatosis, chondromatosis, rarely with hip implants
• Not associated with trauma, although trauma may lead to discovery of tumor
• Sites: metaphysis of long bones (distal femur, proximal tibia, proximal humerus; sites of peak mitotic activity for bone cells); occasionally diaphysis, rarely epiphysis; less common in flat bones or short bones; usually arises within medullary cavity and extends to cortex
• Multicentric: usually children, densely sclerotic by Xray, extremely aggressive, associated with p53 mutations
• Post-radiation: 10-15 years after 40-60 Gy exposure for various conditions; may cause fibrosarcoma, osteosarcoma or MFH; usually high grade, poor prognosis unless can excise with wide surgical margin
• Codman's triangle: shadow between cortex and raised ends of periosteum (due to reactive bone formation), non-specific
• Biopsy: incision should be placed so it will be entirely removed by subsequent excision
• Sites of metastasis: lung (98%, 20-80% at diagnosis, rarely within pulmonary arteries), other bones (37%), pleura (33%), heart (20%), rarely to lymph nodes, GI tract, liver, brain
• Note: excision of metastatic lung nodules may prolong survival

Prognostic factors
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• Poor: associated Paget disease, telangiectatic histology, elevated serum alkaline phosphatase, minimal postchemotherapy tumor necrosis, involvement of craniofacial bones (not jaw) or vertebrae, multifocal tumor, loss of heterozygosity of RB gene
• Good: jaw or distal extremities; solitary; parosteal, periosteal or well differentiated intramedullary histology; extensive necrosis (>95%) after preoperative chemotherapy
• 5 year survival: 70%

Treatment
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• Preoperative chemotherapy is helpful to spare limbs
• MDR1 gene expression may determine chemosensitivity

Xray description
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• Large, destructive, lytic or blastic mass with permeative margins
• May break through cortex and elevate periosteum
• Sunburst pattern due to new bone formation in soft tissue

Radiology images
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Multifocal osteosarcoma

Blastic type, xray - contributed by Dr. Mark R. Wick

CT scan, cuboid bone - contributed by Dr. Mark R. Wick

Distal femur xray - contributed by Dr. Mark R. Wick

Clinical images
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Foot - contributed by Dr. Mark R. Wick

Case reports
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• 15 year old boy with intracortical tumor of tibia (Am J Surg Pathol 1984;8:65)
• 21 year old man with metastases presenting as jejunal polyp (Arch Pathol Lab Med 2000;124:1682)
• 28 year old man with primary osteosarcoma of toe phalanx (Am J Surg Pathol 1988;12:300)
• 65 year old woman with fatal pulmonary embolism (Arch Pathol Lab Med 1999;123:437)
• 66 year old woman with a breast mass (Arch Pathol Lab Med 2003;127:e227)
• Patient with Cowden disease (Arch Pathol Lab Med 1993;117:1252)

Gross description
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• Big, bulky, gritty, hemorrhagic with cystic degeneration
• Spreads within medullary cavity, destroys cortical bone, elevates periosteum and invades soft tissue
• Rarely penetrates joint along tendons/ligaments
• May form satellite nodules (“skip metastases”)
• Usually has well defined proximal and distal margins
• 25% have large amounts of cartilage

Gross images
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Jejunal metastasis

Pulmonary embolus

Hemorrhagic osteosarcoma

Distal femur - contributed by Dr. Mark R. Wick

 

Femur - contributed by Dr. Mark R. Wick

Fibula - contributed by Dr. Mark R. Wick

Micro description
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• High grade spindle cell tumor that produces osteoid matrix unconnected by cartilage (by definition)
• Tumor cells produce neoplastic bone - basophilic thin trabeculae of neoplastic bone resembling fungal hyphae or neoplastic osteoid - eosinophilic, homogenous, glassy with irregular contours and osteoblastic rimming
• Destroys or grows around trabeculae
• Vascular invasion and necrosis common
• May have osteoblastic, fibroblastic (pure spindle cell growth with minimal matrix) or chondroblastic predominance (malignant appearing cartilage with peripheral spindling and osteoid production)
• Osteoid may be variable in amount
• With bizarre giant cells in stroma or acellular stroma
• Vessels may have hemangiopericytoma-like features
• Tumor cells may be spindly, oval or round of variable size
• 25% have osteoblast-like multinucleated giant cells
• Cartilage may be mineralized, immature, myxoid

Micro images
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Osteoblastic

With fascicular growth pattern

 

Chondroblastic

Quiz case

Osteolytic

Implant related tumor

Jejunal metastasis

Vascular invasion in jejunal metastasis

Intracortical osteosarcoma

Foot osteoblastic - contributed by Dr. Mark R. Wick

Low grade sclerosing type - contributed by Dr. Mark R. Wick

Contributed by Dr. Mark R. Wick

Osteoblastic type with blue spiculated bone - contributed by Dr. Mark R. Wick

With infiltrative medullary growth - contributed by Dr. Mark R. Wick

   

Osteoblastic type - contributed by Dr. Mark R. Wick

Virtual slides
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Large destructive lesion

Metastatic osteosarcoma

Cytology images
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FNAB - contributed by Dr. Mark R. Wick

Positive stains
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• Alkaline phosphatase, vimentin, variable smooth muscle actin and desmin, S100 (if chondroid differentiation), vWF (Mod Pathol 2005;18:388), rarely hCG (Arch Pathol Lab Med 1989;113:416)

Negative stains
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• Keratin, EMA

Molecular description
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• Usually aneuploid or hyperploid except periosteal and well differentiated (usually diploid), 20% have p53 mutations

Electron microscopy description
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• Differentiated tumor cells resemble normal osteoblasts with abundant dilated endoplasmic reticulum, rare mitochondria
• Matrix composed of nonperiodic fibrils, scattered collagen fibers, focal calcium deposits of hydroxyapatite crystals

Differential diagnosis
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• Exuberant fracture callus
• Giant cell tumor: unlikely in metaphysis of young patient
• Myositis ossificans

Additional references
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• Mod Pathol 2002;15:878

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