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FPP-MSS > September 11 Bone Path > Flashcards

September 11 Bone Path Flashcards

1
Q

What does a sclerotic margin on a bone Xray mean?

A

Benign, slow growing neoplasm

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2
Q

What does an ill-defined margin on a bone Xray mean?

A

Malignant tumor

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3
Q

What does solid bone on a bone xray mean?

A

Malignant matrix forming tumors

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4
Q

What do rings/arcs on a bone xray mean?

A

Chondroid matrix forming tumors

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5
Q

Ostoid osteoma

A
  • Long bones, femur, tibia, most likely knee
  • <2 cm
  • Night pain
  • Responds to aspirin
  • Radiolucent lesion with a sclerotic cortex
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6
Q

What is this?

A

Cells within an osteoid osteoma or osteoblastoma (hard to tell apart)

New bone cells forming

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7
Q

Osteoblastoma

A
  • tumor in vertebrae, long bone metaphysis
  • >2 cm, painful, not responsive to aspirin
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8
Q

Osteosarcoma

A
  • 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

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9
Q

What is this?

A

Osteosarcoma

Cells in osteoid irregular, tripolar mitosis

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10
Q

Osteochondroma

A
  • 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

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11
Q

What is this?

A

Osteochondroma

Normal cartilage that has calcification and osteoid forming bone AND marrow

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12
Q

Endochondroma

A
  • 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
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13
Q

What is this?

A

Endochondroma

Lobules of hyaline cartilage with minimal atypia (no bone formation)

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14
Q

Ollier’s Disease

A

Multiple enchodromata, regional lesions, skeleton malformation

Multiple chrondromatosis due to pt mutations in IDH1 or IDH2

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15
Q

Maffucci’s Sx

A

Multiple enchondromata AND angiomata

Skeletal malformation and higher risk for malignancy

Multiple chondromatosis–point mutations in IDH1 or IDH2

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16
Q

Chondrosarcoma

A
  • 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

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17
Q

What is this?

A

Chondrosarcoma

More cellular/pleomorphic nuceli than enchondromas

Myoxid changed matrix

18
Q

Non ossifying fibroma

A

Common developmental cortical defect

incidental finding in tibia, femur 0-30

related to eccentric/lytic/peripheral sclerosis

19
Q

What is this?

A

Non-ossifying fibroma

Dense fibrous tissue with collagen

20
Q

Fibrous Dysplasia

A

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

21
Q

What is this?

A

Fibrous Dysplasia

Randomly orientated woven bone “chinese characters” surrounded by fibroblast stroma

22
Q

McCune Albright Sx

A

Polystotic FD with endocrinopathies and cafe au lait spots

  • female > male
  • sexual precocity, acromeagly, Cushing
  • GNAS mutations increase cAMP which increase endocrine gland activity
23
Q

Ewing Sarcoma/PNET

A

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
24
Q

What is this?

A

Ewing Sarcoma/PNET

Small round blue cells with neural phenotype and glycogen that stain with CD99; no bone/cartilage matrix

25
Q

Giant Cell Tumor Bone

A
  • 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
26
Q

What is this?

A

Giant Cell Bone Tumor

27
Q

Metastatic bone tumors in general

A

Most common malignant bone tumor, multiple

70% axial skeleton, lytic

may be bone forming in breast/prostate

Also go to lung, thyroid, kidney

28
Q

How do osteoblasts differentiate?

A

Come from mesenchymal stem cells

Differentiate due to WNT/B catenin making Runx2

Also due to TGFB, BMP, PTH, steroids, IGF, TNF, FGF

29
Q

What are some key markers of osteoblasts?

A

Key marker: collagen I

Fully mature: DMP, SOST, DKK1

*Can use calcium and phosphate to see in vitro if necessary

30
Q

How do we visualize RunX2

A

Alizarin red=shows calcification

alcian blue=shows cartilage

31
Q

Osteoclast maturation

A

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

32
Q

What does SOST do?

A

Expressed by osteocytes to inhibit WNT pathway depending on mechanical load; this stops differentiation of osteoblasts

33
Q

What do we give patients to sense bone growth?

A

Tetracycline (10 days then 5 days before biopsy)

34
Q

What does mechanical load do to SOST expression?

A

Inhibits it; osteoblasts can then go through Wnt pathway and mature

35
Q

How does collagen assuembly work?

A
  • 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
36
Q

Osteogenesis Imperfecta

A

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)

37
Q

What are some markers for bone formation and absorption?

A

Formation: PINP and pyridinoline

Reabsorption: NTX and CTX

38
Q

Osteomalacia

A

Osteoblasts try to make matrix but can’t mineralize due to missing nutrients

Leads to osteoid overgrowth; if during bone development –> RICKETTS and pseudofractures

39
Q

Sclerosteosis

A

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

40
Q

Osteopetrosis

A

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

41
Q

Paget’s Disease

A

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

FPP-MSS (6 decks)

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