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Skeletal system
- 206 bones + joints
- mineralized connective tissue
- - calcium hydroxyapatite
- - cells of bone and osteoid
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Basic Bone Cells
- Osteoprogenitor cells
- •Pluripotent mesenchymal stem cells; bony surfaces.
- •divide and differentiate into osteoblasts when stimulated by growth factors.
- Osteoblasts
- •Synthesize, transport, and arrange protein matrix and initiate mineralization.
- Osteoclasts
- •Responsible for bone resorption
- Osteocytes
- •Control microenvironment calcium and phosphate levels
- •Detect mechanical forces and translate them into biologic activity
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Bone Remodeling Regulators
- RANK (Receptor Activator for Nuclear factor κB)
- •Member of the TNF family
- •Expressed on membranes of pre- and mature osteoclasts.
- •Stimulated by RANKL, leading to activation of NF-κB, which stimulates osteoclasts
- RANK Ligand (RANKL)
- •Expressed by osteoblasts and marrow stromal cells
- •Stimulates RANK
- Osteoprotegerin
- •Blocks the actions of RANKL
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Proteins of Bone Matrix
- Osteoblast-derived proteins - Type 1 collagen
- Cell adhesion proteins - Osteopontin, fibronectin, thrombospondin
- Calcium-binding proteins - Osteonectin, bone sialoprotein
- Proteins involved in mineralization - Osteocalcin
- Enzymes - Collagenase, alkaline phosphatase
- Growth factors - IGF-1, TGF-β, PDGF, CytokinesIL-1, IL-6, RANKL
- Proteins concentrated from serum - β2-microglobulin, Albumin
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Ossification (or osteogenesis) - wiki
- The process of laying down new bone material by osteoblasts. Two types of ossification result in the formation of normal, healthy bone tissue:
- Endochondral ossification - cartilage as the precursor. The formation of long bones and other bones;
- Intramembranous ossification - no cartilage involved, directly lay down bone into primitive connective tissue (mesenchyme); forms the flat bones of the skull, clavicle, and mandible.
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Endochondral Ossification
- Bone grows to replace the cartilage through the epiphyseal plate, which closes in the teenage years, a little earlier in females than males, that is when children become mature skeletally. After that there is no more lengthening of bone.
- Primary ossification center in the center of bone
- Secondary ossification center near the ends
- Proliferating chondrocytes -> maturing cartilage -> hypertrophic cartilage -> calcified cartilage -> bone
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Intramembranous Ossification
- Bone formation directly within fibrous stroma.
- Development of center of Ossification - osteoblast
- Osteocytes deposit mineral salts (calcification) - osteocyte in lacuna, canaliculus, newly calcified bone matrix, together circled by osteoblast.
- Formation of trabeculae - mesenchyme condenses
- Development of periosteum, spongy bone, and compact bone tissue - periosteum contains fibrous layer and osteogenic layer.
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Osteoblast create a type I collagen-containing matrix, osteoid. osteoblasts incorporated in osteoid become osteocytes. Mineralized osteoid containing osteocytes is lined by active osteoblasts.
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BONE TUMORS - Introduction.
- Very diverse and rare group of diseases.
- Accurate diagnosis - essential for survival and maintaining optimal function.
- Correlation with radiological images is of utmost importance.
- Classification is based on cell of origin, connective tissue matrix they produce and differentiation.
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Classification
- Hematopoietic (40%) - [M] Lymphoma, Myeloma;
- Cartilaginous (22%) - [B] Osteochondroma, Chondroma, Chondroblastoma, Chondromyxoid fibroma; [M] Chondrosarcoma;
- Osseous (19%) - [B] Osteoma, Osteoid Osteoma, Osteoblastoma; [M] Osteosarcoma;
- Fibrogenic - [B] Fibrous Cortical Defect, Non-Ossifying Fibroma, Benign Fibrous Histiocytoma, Desmoplastic Fibroma; [M] Pleomorphic Undifferentiated Sarcoma (formerly malignant fibrous histiocytoma);
- Unknown Origin - [B] Giant Cell Tumor, Unicameral Bone Cyst, Aneurysmal Bone Cyst; [M] Ewing Sarcoma;
- Notochordal - [M] Chordoma.
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CLINICAL OVERVIEW OF Bone Forming Tumors
- Common benign lesions - asymptomatic and detected incidentalLY.
- Some tumors - pain (does not always indicate malignancy!) and slow growing.
- First evidence of a tumor may be a pathologic fracture.
- Age matters.
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Plain Radiographs.
- localize and assist in the biopsy of a lesion.
- Osseous lesions must be > 40-50% destructive to be seen on plain films.
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Computed Tomography (CT) Scans and Magnetic Resonance.
- CT Scan - Good for bone but not soft tissue;
- MRI - Good for soft tissue but not bone; Signal Intensities: T1 and T2;
- - Fat - Bright on T1 and Low on T2;
- - Water - Low on T1 and Bright on T2;
- - Blood -Low on T1 and Low on T2;
- - Bone - No signal on T1 and T2.
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INTRODUCTION of SOFT TISSUE TUMORS.
- Proliferations in the extraskeletal, nonepithelial tissues.
- Classified according to the normal tissues they recapitulate (muscle, fat, etc).
- Some have no normal histologic counterpart.
- Benign:malignant = 100:1.
- 8000 sarcomas diagnosed annually in US, responsible for 2% of cancer deaths.
- Vast majority - unknown causes.
- Associations: radiation, chemical/thermal burns, trauma, phenoxyherbicides, chlorophenols.
- Genetic syndromes: neurofibromatosis 1, Gardner syndrome, Li Fraumeni syndrome.
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Location of Soft Tissue Tumors
- Lower Extremity: 40%
- Trunk and Retroperitoneum: 30%
- Upper Extremity: 20%
- Head and Neck: 10%
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Prognostic Information-Staging
- Histologic grade (I-III) - based on pleomorphism, mitoses, cellularity, necrosis;
- Tumor size, location, depth (superficial vs deep), grade, and presence or absence of metastasis;
- For deep sarcomas, 80% >20 cm metastasize, 30% > 5 cm metastasize.
- Overall 10 year survival rate: 40%.
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