Bone Chapter 20

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• Gardner syndrome is associated with osteoma , a bone forming tumor of the head & neck. Occur in the middle age.
• Universal clinical feature of osteoid osteomas is pain relieved by aspirin and that is localized.
• Universal clinical feature of osteblastomas is pain not relieved by aspirin and that is difficult to localize.
• Bone forming tumor located in head & neck is osteoma
• Bone forming tumor located beneath the periosteum or within the cortex in the proximal femur & tibia or posterior spinal elements is osteoid osteomas
• Bone forming tumor located in the vertebral column is osteoblastoma
• Third most common primary malignant tumor located in any bone but mostly the extremitets is osteosarcoma
• Osteosarcoma occurs but 75% of patients are under 20 year old
• Mutations in osteosarcoma inlcudes RB, TP53, MDM2, CDK4, CDKN2A
• Codman triangle A triangular shadow on the x-ray film betw. the cortex and raised periosteum characteristic for osteosarcoma
• Cartilage forming tumor located in the bones of endochondral origin – arising at the metaphysis near the growth plate of long tubular bones (e.g in knee) is ostochondroma and it tend to stop growing once the normal growth of the skeleton is completed. Pelvis, scapula, ribs (sessile), hands and feet (short tubular bones)
• Multiple hereditary osteochondromas (MHO) autosomal dom. disorder where multiple osteochondromas become apparent during childhood,
• Mutation in osteochondroma includes EXT1 & EXT2
• Cartilage forming tumor located in metaphyseal region of tubular bones – especially the the short tubular bones of the hands & feet is chondroma
• Chondroma arising within the medulla is called a enchondromas
• Chondroma arising on the bone surface is juxtacortical chondromas
• Ollier disease multiple chondromas involving one side of the body,
• Maffucci syndrome multiple chondromas assoc. w/ soft tissue spindle cell hemangiomas – inc. risk of malignancy incl. ovarian carcinoma & glioma
• Mutation in chondroma IDH 1 & 2
• O-ring sign chondroma
• storiform (pinwheal) pattern fibrous cortical defect & nonossifying fibroma
• McCune-Albright syndrome Polyostotic disease associated with café au lait spots & endocrinopathies – e.g. sexual precocity (early puberty, girls more often), hyperthyroidism, GH–secreting pituitary adenomas, & primary adrenal hyperplasia.
• Cartilage forming tumor located in the pelvis, shoulder, ribs is chondrosarcoma and has many variants e.g. conventional, myxoid, dedifferentiated, clear cell & mesenchymal.
• Ewing sarcoma & PNETs arises in the medullary cavity & invades the cortex and periosteum ––> to produce a soft tan- white tumor mass, often with hemorrhage & necrosis. e.g. GI tract & ovaries
• small round blue tumors Ewing sarcoma & PNETs
• Benign tumor located in the metaphysis of long bones & posterior elements of vertebral body Aneurysmal bone cysts
• Homer-Wright rosettes are found in ewing sarcoma
• mutations in Ewing sarcoma EWSR1–FLI1, EWSR1–ERG
• mutations in Aneurysmal bone cysts USP6
• Giant cell tumor are also known as osteoclastoma
• Reactive tumor-like lesions occuring near a joint capsule or tendon sheath e.g. in the wrist that can be treated with bible therapy ganglion
• Reactive tumor-like lesions occuring in the popliteal fossa is baker cysts
• acquired (1;2) translocation – that fuses the promoter of the collagen 6A3 gene to the coding sequence of the growth factor M-CSF occurs in Tensynovial giant cell tumor
• Mutation in rhabdymosarcoma t(2:13) – PAX3-FKHR
• Dysostosis dev. abnormality resulting fr. localized problems in the migration of mesenchymal cells and the formation of condensations. May affect individual or a group of bones & can result fr. mutations in specific homeobox genes! Lesions can include... Aplasia = congenital absence of a digit or rib Abnormal fusion of bones (e.g., premature closure of the cranial sutures or congenital fusion of the ribs) → may occur as isolated, sporadic lesions or as components of a more complex syndrome.
• Brittle bone disease w/ blue scleare osteogenesis imperfecta – collagen type 1 defect
• stormiform pattern pleomorphic fibroblastic/sarcoma
• strap cells/ tadpole cells rhabdomyosarcoma
• gland like pattern synovial sarcoma
• leiomyosarcoma spindle cells with cigar shaped nuceli
• Achondroplasia most common form of dwarfism
• Mutations in Achondroplasia FGFR3
• Mutations in Synovial sarcoma t(x;18)(p11;q11) → SS18 gene and one of three SSX genes
• Death loving dwarfism thanatophoric
• Osteopetrosis decreased turnover leads to “bone-that-is-like-stone disorder” – A group of rare genetic disorders that are charact. by defective osteoclast-mediated bone resorption ⇒ leading to bones that are dense, solid, and stone- like
• cause of osteopetrosis (a) Disturbed osteoclast function → unknown in many cases. In some cases by carbonic anhydrase II deficiency, proton pump deficiency & chloride channel defect – all interfere w/ the ability of osteoclasts to resorb bone. (b) interference of osteoclast formation & differentiation → A muse model by mutations in the monocyte-colony stimulating factor (M-CSF), which is required for osteoclast differentiation
• cause of osteoporosis acquired condition characterized by reduced bone mass, leading to bone fragility and susceptibility to fractures – occurs when the dynamic balance between bone formation by osteoblasts and bone resorption by osteoclasts
• Factors that could lead to somone acquiring osteoporosis include age, disuse, postmenopause ,genetics e.g. inability to take up vitamin D or Ca2+ & calcium nutritional state – but also secondary because of prolonged use of glucocorticoids, alcohol & cigarette use.
• mutations in paget disease SQSTMI gene
• " Mosaic pattern (jigsaw puzzle) " paget disease
• cause of osteomalacia manifestation of vitamin D deficiency or its abnormal metabolism Pathogenesis: the fundamental defect is an impairment of mineralization ⇒ resulting in accum. of unmineralized matrix. OBS! Opposite to osteoporosis – that has normal mineral content & decr. total bone mass
• rickets osteomalacia – but in children interferes with the deposition of bone in the growth plates
• Osteomalacia rickets but in adults bone formed during remodeling is undermineralized ⇒ resulting in predisposition to fractures.
• Dissecting osteitis occurs in hyperparathyroidism; increased numbers of osteoclasts boring into the centers of bony trabeculae
• Cortical cutting cones Occurs in hyperparathyroidism; expanding haversian canals
• Brown tumor of hyperparathyroidism osteoclasts, reactive giant cells & hemorrhagic debris form a distinct mass
• Osteitis fibrosa cystica cystic change can be confused with primary bone neoplasms in cases of hyperparathyroidism
• nonunion or pseudoarthrosis Too much motion along the fracture gap causes the central portion of the callus to undergo cystic degeneration; the luminal surface can become lined by synovial-type cells → creating a false joint, normal healing can be achieved only if the interposed soft tissues are removed & the fracture site is stabilized.
• causes of ischemic necrosis (osteonecrosis) Vascular compression or disruption, Steroid administration, Thromboembolic diseasePrimary vessel disease (e.g., vasculitis), Sickle cell crisis
• Subchondral infarcts occurs in osteonecrosis – the overlying articular cartilage also remains viable because the synovial fluid provides nutritive support; initially present with pain during physical activity that becomes more persistent with time.
• Medullary infarcts occurs in osteonecrosis – usually are silent unless large in size (as may occur with Gaucher disease, caisson disease, or sickle cell disease).
• creeping substitution Occurs in osteonecrosis – With time, osteoclasts can resorb some of the necrotic bony trabeculae; any dead bone fragments that remain act as scaffolding for new bone formation
• Sequestrum occurs in osteomyletitis – Non-viable bone, entrapped bone rapidly becomes necrotic
• Involucrum occurs in osteomyelitis – Leukocyte cytokine release stimulates osteoclastic bone resorption, fibrous tissue ingrowth, & bone formation in the periphery. Reactive woven or lamellar bone can be deposited; when it forms a shell of living tissue around a sequestrum
• A destructive lytic focus surrounded by edema & a sclerotic rim is a radiologic finding of Pyogenic Osteomyelitis

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