September 11 Bone Path Flashcards
What does a sclerotic margin on a bone Xray mean?
Benign, slow growing neoplasm
What does an ill-defined margin on a bone Xray mean?
Malignant tumor
What does solid bone on a bone xray mean?
Malignant matrix forming tumors
What do rings/arcs on a bone xray mean?
Chondroid matrix forming tumors
Ostoid osteoma
- Long bones, femur, tibia, most likely knee
- <2 cm
- Night pain
- Responds to aspirin
- Radiolucent lesion with a sclerotic cortex
What is this?
Cells within an osteoid osteoma or osteoblastoma (hard to tell apart)
New bone cells forming
Osteoblastoma
- tumor in vertebrae, long bone metaphysis
- >2 cm, painful, not responsive to aspirin
Osteosarcoma
- malignant mesenchymal tumor that makes bone
- most common bone sarcoma
- metaphysis of long bone (knee)
- Hematogenous spread to lungs
Patho: mutant RB, p53 (Li Fraumeni), too much MDM2/INK4/p16, Paget disease/bone growth diseases, irradiation
Xray: Codman’s triangle; poorly defined, bone/cortical disruption into soft tissue
Prognosis: avg age 5 and 55-80, M>F; 60-65% live past 3-5 yr due to chemo and surgery
What is this?
Osteosarcoma
Cells in osteoid irregular, tripolar mitosis
Osteochondroma
- most common benign tumor of bone
- metaphysis
- malignancy chance increases with herditary multiple exotoses
- autosomal dominant (EXT 1 8q24 mutations)
Clinically: little bleb off side of cortex with marrow and cartilage cap
What is this?
Osteochondroma
Normal cartilage that has calcification and osteoid forming bone AND marrow
Endochondroma
- Benign hyaline cartilage lesion
- Endochondroma=intramedullary, periosteal=juxtacortical (under periosteum)
- Asym.
- Appendicular skeleton, small bones hands and feet
- Xrays=lytic, lobulated, cortical thinning
- Tx=none unless symptomatic or growth after skeleton matures
What is this?
Endochondroma
Lobules of hyaline cartilage with minimal atypia (no bone formation)
Ollier’s Disease
Multiple enchodromata, regional lesions, skeleton malformation
Multiple chrondromatosis due to pt mutations in IDH1 or IDH2
Maffucci’s Sx
Multiple enchondromata AND angiomata
Skeletal malformation and higher risk for malignancy
Multiple chondromatosis–point mutations in IDH1 or IDH2
Chondrosarcoma
- Malignant tumor; neoplastic cells make cartilaginous matrix
- 2nd most common bone sarcoma
- Older adults ages 60-70
- Central skeleton, humerus, femur
Imagining: medullary calcifications, cortical erosion/destruction, “popcorn”
Variant: de-differentiated=losing chondrad differentiation
What is this?
Chondrosarcoma
More cellular/pleomorphic nuceli than enchondromas
Myoxid changed matrix
Non ossifying fibroma
Common developmental cortical defect
incidental finding in tibia, femur 0-30
related to eccentric/lytic/peripheral sclerosis
What is this?
Non-ossifying fibroma
Dense fibrous tissue with collagen
Fibrous Dysplasia
Developmental arrest of bone
Monostatic=adolescents (rib, mandible, femur)
Polyostatic=infancy/childhood (crippling deformities, facial)
*includes McCune Albright Sx
Clinical: expansile, circumsized, thin cortex; looks like ground glass
What is this?
Fibrous Dysplasia
Randomly orientated woven bone “chinese characters” surrounded by fibroblast stroma
McCune Albright Sx
Polystotic FD with endocrinopathies and cafe au lait spots
- female > male
- sexual precocity, acromeagly, Cushing
- GNAS mutations increase cAMP which increase endocrine gland activity
Ewing Sarcoma/PNET
Second most malignant bone tumor in kids
- adolescents/young adults M>F –> diaphysis long tubular bones, ribs, pelvis
- painful enlarging mass
- Xray=moth eaten medullary lesion with large soft tissue mass; onion skin pattern periosteal growth (lines on xray)
- Pathogenesis: t11;22; EWS on 22q fused with FLI-1 factor on 11q
What is this?
Ewing Sarcoma/PNET
Small round blue cells with neural phenotype and glycogen that stain with CD99; no bone/cartilage matrix
Giant Cell Tumor Bone
- Young adults 20-40, F>M
- Epiphyseal in knee, proximal humerus, radius
- Benign but locally aggressive…can destroy cortex of bone and go into soft tissue
What is this?
Giant Cell Bone Tumor
Metastatic bone tumors in general
Most common malignant bone tumor, multiple
70% axial skeleton, lytic
may be bone forming in breast/prostate
Also go to lung, thyroid, kidney
How do osteoblasts differentiate?
Come from mesenchymal stem cells
Differentiate due to WNT/B catenin making Runx2
Also due to TGFB, BMP, PTH, steroids, IGF, TNF, FGF
What are some key markers of osteoblasts?
Key marker: collagen I
Fully mature: DMP, SOST, DKK1
*Can use calcium and phosphate to see in vitro if necessary
How do we visualize RunX2
Alizarin red=shows calcification
alcian blue=shows cartilage
Osteoclast maturation
Hematopoietic origin
Need 2 signals: RANKL and CSF 1
Osteoblasts release RANK L –> osteoclasts into multinucleated giant cell –> secrete cathesin K, “sealing zone/ruffled border”, HCL to break bone
*osteoblasts can also make inhibitors to RANK L
What does SOST do?
Expressed by osteocytes to inhibit WNT pathway depending on mechanical load; this stops differentiation of osteoblasts
What do we give patients to sense bone growth?
Tetracycline (10 days then 5 days before biopsy)
What does mechanical load do to SOST expression?
Inhibits it; osteoblasts can then go through Wnt pathway and mature
How does collagen assuembly work?
- starts as left handed triple helix Gly-x-y (x and y are proline/hydroxyprline)
- Self assembles in ER, zip from C terminus to N termius and cleaves ends
- Procollagen to tropocollagen with 67 nm spaces (collagen 1=two alpha1 chains, one alpha2 chain)
- Cross links lysine with Vit C dpt manner to get pyridinoline and hydroxypyridinoline aromatic strong cross links
- collagen –> collagen fibril –> collagen fibers –> lamellae –> cortical and trabecular bone
Osteogenesis Imperfecta
Disease arising from defective synthesis of bone
Collagen fibrils end up bent due to COL1A1g748c mutation
Causes:
Fractures, bending bone, growth retardation, wheelchair bound, hearing issues, fragile skin (because type 1 collagen defect in skin too)
What are some markers for bone formation and absorption?
Formation: PINP and pyridinoline
Reabsorption: NTX and CTX
Osteomalacia
Osteoblasts try to make matrix but can’t mineralize due to missing nutrients
Leads to osteoid overgrowth; if during bone development –> RICKETTS and pseudofractures
Sclerosteosis
Wnt pathway not properly regulated due to SOST mutation
Excessive growth of bone
Nerve entrapment (narrow pts in skull for CN to get through) leads to facial palsy, deafness, syndactyly
Osteopetrosis
Osteoclasts can’t reabsorb bone –> osteoclast malfunction
Bone can’t remodel (so become weak), ttooth eruption issues; if severe, not enough space fo hematopoesis
Left with woven/primary bone
Paget’s Disease
Too much remodeling/turnover of bone=weakened, bowing, enlargement, pain, nerve entrapment, woven bone
Blastic phase: serum alkaline phosphatase increase
Lytic phase: urinary hydroxyproline increases
People predisposed to osteosarcoma
