Bone pathology Flashcards
1
Q
What kinds of bones develop from intramembranous ossification?
A
- flat bones: formation of bone without a preexisting cartilage matrix
- the others do endochondral ossification… mostly long bones
2
Q
If someone has short thumb and big toe, what gene is messed up?
A
-HOXD13
3
Q
What is cleidocranial dysplasia?
A
- LOF mutation in RUNX2
- patent fontanelles
4
Q
Achondroplasia
A
- impaired cartilage proliferation in the growth plate
- common cause of dwarfism
- short extremities
- intramembranous bone not affected
- mental function, life span, and fertility are not affected
5
Q
mutation in achondroplasia
A
- activating mutation in FGFR3
- overexpression inhibits growth
- most mutations are sporadic
6
Q
Thanatophoric dysplasia
A
- mot sommon lethal form of dwarfism
- bell shaped abdomen
- shorened limbs, frontal bossing, macrocephaly…
- die at birth or soon after
- also GOF FGFR3 mutation, but different from achondroplasia
7
Q
Osteogenesis Imperfecta
A
- congenital defect of bone fomration resulting in structurally weak bone
- Auto dominant defect in Collagen type 1 synth
8
Q
Clinical features of OI?
A
- multiple fractures of bone
- blue sclera: thinning of scleral collagen reveals underlying choroidal veins
- hearing loss: bones in the middle ear easily fracture
9
Q
Gene defect in OI
A
-COL1A1 or 2
10
Q
Which subtype of OI is especially lethal?
A
- type 2
- that is the only predominantly auto recessive one, the other 3 are dominant
11
Q
Osteopetrosis
A
- inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily
- due to poor osteoclast function
12
Q
mutation of what enzyme is in osteopetrosis?
A
- carbonic anhydrase 2 (makes carbonic acid from H20 and CO2)
- loss of acidic environment needed for bone resorption
13
Q
clinical features of osteopetrosis
A
- bone fractures
- pancytopenia… bony replacement of the marrow (myelophthisic process)
- vision and hearing impairment.. impinges CN’s
- renal tubular acidosis: we can’t reabsorbe bicarb now… metabolic acidosis
14
Q
Tx for osteopetrosis
A
- bone marrow transplant!
- osteoclasts are derived from monocytes
15
Q
another name for osteopetrosis
A
-alber-schonberg disease
16
Q
What big morphology buzzword is for osteopetrosis
A
-erlenmeyer flask
17
Q
Genetic defect for osteopetrosis
A
- auto dominant: LRP5… hearing loss
- Infantile form: RANKL (auto recessive)
18
Q
Mucopolysaccharaidoses
A
- they accumulate inside chondrocytes… apoptosis
- abnormalities in hyaline cartilage
19
Q
difference between osteopenia nad osteoporosis?
A
- osteoporosis is bone mass 2.5 sd’s lower than mean peak bone mass
- oseopenia is 1-2.5
20
Q
most common forms of osteoporosis?
A
-senile and postmenopausal forms
21
Q
What is osteoporosis
A
- reduction in trabecular bone mass
- results in porous bone with an increased risk for fracture
- risk of oseoporosis is based on peak bone mass and rate of bone loss that follows after
22
Q
clinical features of osteoporosis
A
- bone pain and fractures in weight-bearing areas like the vertebrae, hip, and distal radius
- bone density is measured using a DEXA scan
23
Q
How are the serum calcium, phosphate, pth, and alk phos levels in osteoporosis?
A
- NORMAL
- this helps to exclude osteomalacia which is nice because it’s like the same presentation
24
Q
Tx of osteoporosis
A
- exercise, vti D, and Ca2+
- Bisphosphonates: induce apoptosis of oseoclasts
- Estrogen replacement therapy is debated
- glucocorticoids are contraindicated (worsen osteoporosis)
25
gene defect for osteoporosis-pseudoglioma syndrome?
- LRP5
| - infant onset loss of vision, skeletal fragility
26
gene defect for osteopetrosis with renal tubular acidosis
-CA2
27
gene defect for osteopetrosis, late onset type 2?
- CLCN7
| - chloride channel, increased bone density, fragility
28
What are the top genetic factors for osteoporosis?
-RANKL, OPG, and RANK
29
hallmoar of osteoporosis?
-histologically normal bone that is decreased in quantity
30
where in the body will we see the effects of postmenopausal osteoporosis the most?
-vertebral bodies or bones that have a lot of surface area
31
is measurement of blood levels of Ca2+, Phosphorous, and alk phos diagnostic for osteoporosis?
- no!
| - remember those labs are normal
32
Paget Disease (osteitis deformans)
-imbalance betwen osteoclast and osteoblast function
-late adulthood... old ppl
-localized process involve one or more bones: DOES NOT INVOLVE THE ENTIRE SKELETON
-
33
What gene involvement is shared between OI and dermatofibrosarcoma protuberans?
- COL1A1
| - remember in the derm one, it's a translocation between COL1A1 and PDGFB
34
What are the 3 stages of paget disease of bone?
- osteoclastic
- mixed osteoblastic-clastic
- osteoblastic
35
What is the end result of paget disease
- thick, sclerotic bone that fractures easily
| - biopsy reaveal a MOSAIC pattern of lamellar bone
36
Clinical features of paget diseas
- bone pain: microfractures
- increasing hat size: skull is commonly affected
- hearing loss: impinging CN's
- lion-like facies: involvement of craniofacial bones
- isolated elevated alk phos
37
What is the most common cause of isolated elevated alk phos in patients >40 y/o?
-Paget disease of bone
38
Tx of paget disease
- calcitonin: inhibits osteoclast function
| - disphosphonates: induces apoptosis of osteoclasts
39
Complications of Paget disease
- high-output cardiac failure: due to formation of AV shunts in bone
- osteosarcoma
40
gene mutation for paget disease
- SQSTM1 gene
| - increased activity of NFKB....increases osteoclast activity
41
how will the osteoclasts look in paget disease?
- abnormally large
| - more than normal 10 to 12 nuclei, sometime 100!
42
What region of the body is involved with paget disease?
- axial skeleton or prox femur
| - can have leontiasis ossea (lion face)
43
How will the femurs look in pagets disease?
-weight bearing causes anterior bowing of the femurs
44
How will the skin look and feel in pagets?
-warms overlying skin bc hypervascularity
45
labs for someone with pagets?
- elevated serum alk phos
| - normal serum Ca2+ and phosphorous
46
Ricketts
- defective mineralization of osteoid
- low vit D... leads to low Ca and P
- this one is with children
- pigeon breast deformity
- fronal bossing
- rachitic rosary
- bowing of the legs
47
what is the common theme is ricketts problems?
-deposition of osteoid in places
48
Osteomalacia
- low Vit d in Adults
| - bad mineralization... weak bone... increased risk for fracture
49
lab findings for osteomalacia
- low Ca2
- low P
- high PTH
- high alk phos: happens when there is osteoblasts activated
50
If we have hyperparathyroidism, what three skeletal abnormalities will be there?
- osteoporosis: more severe in phalanges, vertebrae, and proximal femur
- brown tumors: vascularity, hemorrhage, and hemosiderin
- osteitis fibrosa cystica
51
What does BMP-7 induce?
- osteoblast differentiation
| - secreted by kidneys
52
FGF-23
- made by osteocytes
| - acts on kidney to regulate phosphate homeostasis and vit D production (dependent on Klotho)
53
simple fracture
-skin is intact
54
compund
-bone communicates with the skin
55
comminuted
-bone is fragmented
56
displaced
-ends of the bone at the fracture site are not aligned
57
stress
-slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to repetitive loads
58
greenstick fracture
-extending only partially through the bone, common in infants when bones are soft
59
pathologic fracture
-involves bone weakened by an underlying disease process, such as a tumor
60
is the cortex normally affected by avascular necrosis?
- no
| - the trabecular bone and marrow are though
61
Osteomyelitis
- infection of marrow and bone
- usually in children
- bacterial usually, arises via hematogenous spread
- transient bacteremia seeds metaphysis (children)
- open wound bacteremia seeds epiphysis (adults)
62
causes of osteomyelitis
- Staph aureus... most common
- N gonorrhoea: sex ppl
- salmonella: sickle cell
- pseudomonas: Diabetic or IV drug abusers
- pasteurella: dog or cat bite
- Mycobacterium tuberculosis: usually involves vertebrae (pott disease)
63
clinical features of osteomyelitis
- bone pain with systemic signs of infection
- lytic focus surrounded by sclerosis of bone on x ray, lytic focus is called sequestrum, and sclerosis is called involucrum
64
brodie abscess
-small IO abscess that frequently involves the cortex and is walled off by reactive bone
65
Sclerosing osteomyelitis of Garre
- jaw
| - extensive new bone formation that obscures much of the underlying osseous structure
66
How is the diagnosis of osteomyelitis made?
-by blood culture
67
What will skeletal syphyllis look like?
- saber shins
- see it on silver histochemical stains
- gummas
68
Avascular septic necrosis
- ischemic necrosis of bone and marrow
- causes include trauma or fracture, steroids, sickle cell anemia, and caisson disease
- osteoarthritis and fracture are major complications`
69
Osteoid osteoma
-benign tumor of osteoblasts surrounded by a rim of reactive bone
-young adults
-cortex of long bones
-
70
presentation of osteoid osteoma
- bone pain that RESOLVES WITH ASPIRIN
- imagin: bony mass with a radiolucent core
- appendicular skeleton
71
How is osteoid osteoma different from osteoblastoma?
-osteoblastoma is similar to this but it's larger (>2cm), arises in vertebra, and presents as bone pain that DOES NOT RESPOND TO ASPIRIN
72
What does the osteoid osteoma and osteoblastoma look like
-round to oval masses of hemorrhagic gritty tan tissue
73
Osteosarcoma
- Malignant proliferation of osteoblasts
- teens
- pathologic fracture or bone pain with swelling
74
Imaging for osteosarcoma
- sunburst
| - codman triangle
75
risk factors for osteosarcoma
-familial retinoblastoma, paget disease, and radiation exposure
76
Where does osteosarcoma arise?
-in the metaphysis of long bones, usually the distal femure or proximal tibia (the knee!)
77
biopsy for osteosarcoma
-pleomorphic cells that produce osteoid
78
What genes will be mutated in osteosarcoma?
- RB: negative regulator of cell cycle
- TP53 (li fraumeni)
- INK4a (inactivated)
- MDM2 and CDK3: inhibit p53 and RB function
79
what is diagnositc for osteosarcoma?
-formation of bone by tumor cells
80
What is an osteosarcoma called when malignant cartilage is abundant?
-chondroblastic osteosarcoma
81
Where does osteosarcoma like to spread to?
-the lungs! hematogenously
82
Morphology of osteosarcomas?
- bulky tumors that are gritty, gray-white
| - remember that osteomas were gritty tan colored
83
outcome for osteosarcoma patients with metastases?
-poor
84
Osteochondroma
- tumor of bone with an overlying cartilage cap; most common benign tumor of bone
- arises from a lateral projection of the growth plate (metaphysis); bone is continuous with the marrow space
- overlying cartilage can transform (rarely) to chondrosarcoma
85
pathogenesis of osteochondroma
- reduced expressiong of EXT1 or EXT2
| - these genes encode enzymes that synthesize heparan sulfate glycosaminoglycans
86
What is another name for osteochondroma?
-exostosis
87
When do osteochondromas stop growing?
-at the time of growth plate closure... makes sense because it comes from the metaphysis
88
Chondroma
- benign tumor of cartilage
| - usually arises in the medulla of small bones of the hands and feet
89
What 2 syndromes have multiple enchondromas?
- Maffucci syndrome and Ollier disease
| - Maffucci also has spindle cell hemangiomas
90
pathogenesis of chondromas
- heterozygous mutations in the IDH1 and IDH2 genes
- encode 2 isoforms of isocitrate dehydrogenase... leads to synth of 2-hydroxyglutarate
- that is an oncometabolite... interferes with regulation of DNA methylation
91
If someone has maffucci syndrome, what else are they at risk for?
-other types of malignancies like ovarian carcinomas and brain gliomas
92
Chondrosarcoma
- malignant cartilage-forming tumor
| - arises in medulla of the pelvis or central skeleton
93
What is special about the clear cell variant of chondrosarcoma?
-it originates in the epiphyses of long tubular bones
94
What is a dedifferentiated chondrosarcoma
-low grade chondrosarcoma with a second, high grade component that does not produce cartilage
95
presentation of chondrosarcomas
-painful, progressively enlarging masses
96
where do chondrosarcomas spread to?
-hematogenously to the lungs
97
Ewing sarcoma
- malignant proliferation of poorly-differentiated cells derived from neuroectoderm
- arises in the diaphysis of long bones; usually in male children
- onion skin appearance on x ray
98
what will biopsy show us for ewing sarcoma?
- small, round blue cells that resemble lymphocytes
| - can be confused with lymphoma or chronic osteomyelitis
99
What is the characteristic tranlocation for ewing sarcoma?
- 11,22
| - EWS (22) and FLI1 (11) genes
100
How does ewing sarcoma often present?
- with mets
| - responsive to chemo
101
what gives us a clue that ewing sarcoma has a greater degree of neuroectodermal differentiation?
-homer-wright rossettes
102
What is an important prognostic finding for ewing sarcomas?
-the amount of chemo induced necrosis
103
Giant cell tumor
- comprised of multinucleated giant cells and stomal cells
- occurs in young adults
- arises in epiphysis of long bones, usually the distal femur or prox tibia (knee)
- soap bubble appearance on x ray
- locally aggressive, may recur
104
what is a synonym for giant cell tumor?
- osteoclastoma
| - often destroy the overlying cortex
105
morphology for giant cell tumor
- sheets of uniform oval mononuclear cells and numerous osteoclast-type giant cells
- the tumor cells do not synthesize bone or cartilage, but reactive bone may be present at the periphery
106
anuerysmal bone cyst (ABC)
- tumor characterized by multiloculated blood-filled cystic spaces
- eccentric, expansile lesion with well-defined margins
107
pathogenesis of ABC
- rearrangements of chormosome 17p13
- results in fusion of coding region of USP6 to promoters of genes that are highly expressed in osteoblasts... leads to USP6 overexpression
108
What is USP67
- encodes ubiquitin specific protease... regulates activity NFKB
- so a lot of NFKB floating around
- that upregulates metalloproteases that lead to cystic resorption of bone
109
morphology of ABC
-multiple blood filled cystic spaces separated by thing, tan-white septa
110
What is fibrous dysplasia?
-all components of normal bone are present, but they do not differentiate into mature structures
111
What is Mazabraud syndrome
- fibrous dysplasia
| - soft tissue myxomas
112
McCune -Albright syndrome
-polyostotic disease with cafe-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty
113
what is the mutation for fibrous dysplasia?
- GOF in GNAS1
- also mutated in pituitary adenomas
- make a constitutively active Gs ptn
