M2 2004 Bone Pathology I

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Bone Pathology I Non-Neoplastic Lesions of Bones and Joints:

Bone Pathology I Non-Neoplastic Lesions of Bones and Joints Richard Anderson, MD President, Associated Pathology Consultants, S.C. Edward Hospital & Elmhurst Memorial Hospital Clinical Instructor, Department of Pathology, UIC College of Medicine Chairman of the Board, Heartland Blood Centers UIC M2 Pathology - 2004

Metabolic Bone Diseases:

Metabolic Bone Diseases Osteoporosis Osteomalacia and Rickets Hyperparathyroidism


Osteoporosis Metabolic disease characterized by diffuse skeletal lesions due to a decreased mass of normally mineralized bone Post-menopausal females Increased bone resorption (osteoblastic activity is normal) Estrogen may lead to increased secretion of IL-1, IL-6, TNF and MCSF by stromal cells which will stimulate osteoclasts


Osteoporosis Primary osteoporosis Some genetic basis Dependent upon levels of Ca ++ and vitamin D Exercise Secondary osteoporosis Corticosteroid excess (endogenous or exogenous) Hyperthyroidism Hypogonadism Multiple myeloma PTH-secreting tumors Malabsorption Alcoholism

Osteomalacia and Rickets:

Osteomalacia and Rickets Accumulation of unmineralized bone matrix resulting from a diminished rate of mineralization Causes: Dietary deficiency in vitamin D Defective bone mineralization Congenital or acquired defects in vitamin D or phosphate metabolism Malabsorption (most common cause in US) Crohn’s disease Celiac disease Cholestatic liver disease Biliary obstruction Chronic pancreatitis


Hyperparathyroidism Increased bone resorption secondary to increased PTH Classic pathologic change referred to as osteitis fibrosa cystica Replacement of marrow by fibrous tissue Numerous microfractures Hemosiderin-laden macrophages Eventually cystic degeneration and classic gross appearance referred to as “brown tumor”

Paget’s Disease of Bone:

Paget’s Disease of Bone Initial osteoclastic activity due to defective remodeling followed by disorganized hyperplastic bone formation Etiology uncertain (viral infection?) M > F Most patients > 55 years Most commonly involves lumbosacral spine, pelvis and skull; very rare in ribs Usually polyostotic Pain

Complications of Paget’s Disease:

Complications of Paget’s Disease Fractures Degenerative arthritis Bone tumors (osteosarcoma, fibrosarcoma, chondrosarcoma and GCT) High-output cardiac failure

Osteogenesis Imperfecta:

Osteogenesis Imperfecta Group of autosomal dominant disorders of connective tissue caused by mutations in the gene for type 1 collagen Patients suffer from repeated fractures Blue sclera (except in subtype IV)

Bone Fractures:

Bone Fractures

Bone Fractures:

Bone Fractures Hematoma Organization with neovascularization (2-3 days) Intramembranous bone growth (7 days) Pluripotential mesenchymal cells give rise to osteoblasts to synthesize woven bone Endochondral ossification Remodeling (months) Lamellar bone

Osteopetrosis (marble bone disease, Albers-Schönberg disease):

Osteopetrosis (marble bone disease, Albers-Sch önberg disease) Inherited lysosomal defect Most severe form (autosomal recessive) is severe and often lethal Death secondary to anemia, cranial nerve entrapment, hydrocephalus and infection Dense bones weighing 2-3 times normal TX with BMTx and IFN- 


Osteomyelitis Bacterial infection of bone Coagulase-positive Staph (70-90% of cases) Klebsiella Pseudomonas (“tennis shoe” osteo) Neisseria Salmonella (SCD) TB Local, exogenous or hematogenous infection Dead bone (“sequestrum”) is surrounded by new bone formation (“involucrum”) Chronic osteomyelitis often requires surgery

Fibrous Dysplasia:

Fibrous Dysplasia Non-neoplastic condition Monostotic variety Older children and young adults May involve rib, femur, tibia and skull Polyostotic variety Unilateral distribution associated with endocrine dysfunction, precocious puberty in females and areas of cutaneous hyperpigmentation ( McCune-Albright syndrome )

PowerPoint Presentation:

Misshapen bony trabeculae interspersed with fibrous tissue

PowerPoint Presentation:

Woven bone NEVER is transformed to lamellar bone

Fibrous Dysplasia:

Fibrous Dysplasia May be complicated by malignancy Osteosarcoma, chondrosarcoma and MFH Treat with surgical curettage and repair of fractures

Pathology of Joints and Synovial Membranes:

Pathology of Joints and Synovial Membranes Osteoarthritis Rheumatoid arthritis Spondyloarthropathies Gout Pseudogout


Osteoarthritis Most common form of joint disease Slowly progressive Elderly or status post trauma Cartilage attrition may be due to IL-1

Rheumatoid Arthritis:

Rheumatoid Arthritis Chronic systemic disease of unknown etiology Joints of hands and feet nearly always involved; may involve elbows, knees, ankles, hips, spine and TMJ F > M (3:1) 4 th to 6 th decade Prevalence 0.5 – 1% Strongly associated with HLA-DR4 and several non-MHC genes

Rheumatoid Arthritis:

Rheumatoid Arthritis Rheumatoid Factor Positive in 70-80% of patients with classic RA Autoantibodies of IgM, IgG or IgA class that react with F c region of IgG Not specific for RA Circulating complexes bind complement Synovial hyperplasia driven by IL-1

PowerPoint Presentation:

Rheumatoid nodules are present in 25% of patients


Spondyloarthropathies Ankylosing spondylitis Vertebral column and sacro-iliac joints Reiter syndrome Post-venereal Urethritis, conjunctivitis and seronegative polyarthritis HLA-B27



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