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Skin MS: Week 6 > Pathology of Bone > Flashcards

Flashcards in Pathology of Bone Deck (126):
1

Non-neoplastic Bone Disease

Fractures of healthy bone

Osteoporosis (especially post-menopausal and senile types) - and associated fractures

Osteomalacia

Osteomyelitis

Avascular (aseptic) bone necrosis/infraction

Paget's disease of bone

Congenital bone disorders 

2

If see osteopenia (generalized decrease in bone mineralization) - Diff dx

Osteoporosis, osteomalacia, malignancy, rare hereditary disorders

3

Neoplasms involving bone

metastatic tumors to skeleton

hemic malignancyes (myeloma/plasmacytoma or lymphoma, acute leukemia) 

4

Primary bone tumor/tumor-like lesions

Benign and malignant

Relatively uncommon (more common in children)

5

Misc. tumor-like diseases which can involve bone

•Histiocytosis X (Langerhan's histiocytosis)
•Mast cell disease
•Hyperparathyroidism (osteitis fibrosa cystica)
•Others:  bone cysts, fibrous dysplasia

6

Pathological fracture 

•fracture through diseased bone—usually refers to fracture through tumorous or tumor-like bone

7

Periosteum pathologically

painful when irritated (trauma, injury), also lays down bone --> thickening of bone

8

Serum alkaline phosphatase 

Marker for osteoblastic disease, also liver disease w/ bile obstruction  (in kids, worry about osteoblastic bone disease - adults, more likely liver defect)

If no other liver lab markers elevated, older person w/ elevated SAP -- Paget's

9

Osteoporosis - ____ faster than _____

Osteoclasts (resorption) faster than osteoblasts (bone building)

10

Biggest danger to kids w/ trauma near epiphyseal plateor osteomyelitis

 Disrupt epiphyseal cartilage (blood vessel invasion) --> stop growth

11

Decreased serum Ca (free) --> 

increased parathyroid hormone --> increase bone resorption --> increase serum calcium 

12

Vit D sources

diet and skin synthesis

 

*** Issues w/ no sun and malabsorption 

13

Vit D processing 

Skin synthesis, liver metabolism, kidney/PTH --> Vitamin D (OH)2 - active in skeleton

 

Renal Disease --> Major skeletal consequences

14

Kidney + PTH --> 

increased production of Vit D(OH)2, tubular resorption of Ca++, tubular excretion of phosphate

15

Required for normal mineralization of bone osteoid

Vit D(OH)2

16

For healthy bone, need 

Ca, P (diet)

Vit D (diet, skin synthesis)

gut (absorbing Ca, P, Vit D)

kidney (makes Vit D (OH)2, resorbs/excretes Ca, P)

parathyroids (master gland for Ca, bone metabolism)

17

High serum ca

Needs to be explained (hyperparathyroidism or cancer?)

18

Steps of Bone healing

Blood clot in fracture site, ingrowth of fibrous tissue, neovascularization

Near fracture --> knows needs to become cartilaginous - then osteocartilaginous - then bone again

Cartilage callus --> woven bone callus --> remodeling into good bone

19

Complications of fractures through healthy bone

Mal-alignment

Non-union/mal-union/pseudoarthrosis

Osteomyelitis (compound fractures)

Growth disturbance (epiphyseal plate injury in children)

Arthritis (if fractures affects articular surface)

Fat embolism syndrome (w/in days of fx)

Immobilization complications (thrombophlebitis/thromboembolism, osteoporosis of immobilized bone)

20

Type of osteopenia d/t bone atrophy caused by imbalance of bone remoding process 

Osteoporosis

21

Osteoporosis: clinical manifestations

no clinical manifestations until fracture - often trivial injury fractures 

Vertebral fractures most common - compression usually acute/painful but wedge fracture usually painless

22

Types/Associations of Osteoporosis

•POSTMENOPAUSAL/SENILE types

•Due to excess corticosteroids (endogenous or exogenous)

•Hyperparathyroidism (slow leech)

•Hyperthyroidism (measure TSH)

•Poor nutrition/malabsorption 

•Immobilization

•Hypogonadism 

•Multiple other disease associations

23

Ability of kidneys to ___________ becomes impaired with age

hydroxylate Vit D(OH)1 to Vit D(OH)2

24

Age/menopause /w osteoporosis 

•Diminished PTH secretion by parathyroid glands in response to hypocalcemic stimulus (post-menopausal patients)

•Increased osteoclastic activity upost-menopausal women

•Decreased ability of osteoblasts to make matrix

25

•Common osteoporosis = diagnosis of _______

Remember the often more treatable / reversible causes of ________

Decreased bone mineralization (osteopenia) ___________ osteoporosis

•Common osteoporosis = diagnosis of exclusion

Remember the often more treatable / reversible causes of secondary osteoporosis

Decreased bone mineralization (osteopenia) does not automatically = osteoporosis

26

Biggest complication of kyphosis

Shrinking thoracic cavity - difficult clearing of lung - pneumonia/infection 

27

Major historical risk factors for osteoporosis in women

•Postmenopausal (within 20 years after menopause)

•White or Asian

•Premature menopause

•Positive family history

•Short stature and small bones

•Leanness

•Low calcium intake

•Inactivity

•Nulliparity

•Gastric or small-bowel resection

•Long-term glucocorticoid therapy

•Long-term use of anticonvulsants

•Hyperparathyroidism

•Thyrotoxicosis

•Smoking

•Heavy alcohol use

28

Most common fractures in osteoporosis (appendicular)

Proximal femur (intertrochanteric or intracapsular), proximal humerus, distal radius (colles')

29

Preventrion osteoporosis

umaximize peak bone mass (teens/young adults)

uencourage weight-bearing exercise and Ca supplementation

30

Labs osteoporosis

•to exclude secondary causes of osteoporosis/osteopenia

- serum Ca, P, alkaline phosphatase, 250H–Vit D, TSH, sometimes PTH (renal insufficiency or malabsorption)

31

Testing osteoporosis

Bone desnitometry

uoffer to all women >= 65 yrs and to any woman <65 yrs if risk factors or unexplained fractures present

32

Most anti-osteoporosis meds ______

inhibit bone resorption

33

Osteoporosis: Biochemical serum markers of bone formation and resorption:

currently NOT sufficiently standardized or studied to provide meaningful diagnostic or therapeutic guidance for individual patients

34

Primary hyperparathyroidism

•Hypercalcemia due to primary hyperplasia or NEOPLASTIC enlargement of parathyroid glands

35

Bony clinical presentation of primary hyperparathyroidism 

•Spectrum of bony changes due to variable degrees of osteoclastic bone resorption—ranging from subtle subperiosteal cortical erosions to diffuse osteoporosis to tumor-like skeletal change (osteitis fibrosa cystica/"Brown tumor")

•Favors resorption of cortical bone over trabecular bone

 

Measure PTH levels

***Used to find these cases w/ renal failure

36

Primary hyperparathyroidism pathology

•:  osteoclastic bone resorption/peritrabecular fibrosis = osteitis fibrosa

37

Primary hyperparathyroidism complications

Fractures

Constitutional symptoms; metabolic impairment of kidneys; muscle weakness; neuropsychiatric syndromes (all direct effects of ­ Ca++)

Renal stone disease

 

•NOTE:  Secondary hyperparathyroidism (renal disease) may also produce gross skeletal change.

38

Prognosis - primary hyperparathyroidism

Good - remove adenoma, reversible

39

Screening hyperparathyroidism

asymptomatic and detected on biochemical screening studies
primary type — ­Ca  and  ¯P

40

Hypercalcemia major causes (from labs)

90% of all cases due to malignancy and hyperparathyroidism

41

Decreased bone mineralization w/ excess osteoid

Osteomalacia

42

Osteomalacia - d/t 

interference w/ calcium, phosphate, or vitamin D metabolism (need to know what's causing that interference)

43

Osteomalacia: Radiologically appears ________

osteopenic (like osteoporosis)

44

Osteomalacia: May present w/ ____________

diffuse skeletal pain (without fracture) - vs osteoporosis (sxs w/ fracture)

45

Osteomalacia associations 

Environmental:  classic childhood rickets
–Poor diet; ¯ sun exposure in northern latitudes
Intestinal malabsorption—commonest cause of Vit D deficiency in USA (celiac?)
Liver or renal disease (impaired hydroxylation of Vit D)
Rare congenital/inborn errors of metabolism
–Deficient Vit D hydroxylation
–Renal tubular phosphate leak
–End organ resistance to Vit D (OH)2

46

Osteomalacia biochemical profile 

•­serum alkaline phosphatase (>90%)

•Low serum Ca or P (50%)

•Decreased urinary Ca excretion (33%)

•­PTH (40%) - not as high as in hyper PTism

•Decreased 1, 25 dihydroxyvitamin D3 (50%)

47

Classic rachitic picture (children)

Widened/distorted growth plates

Bowed legs due to softened bone

Fractures

 

 

48

Renal osteodystrophy/osteomalacia:

Due to progressive destruction of second hydroxylation step of Vit D
 
Most commonly a combination of 2° hyper-parathyroidism as well as abnormal  mineralization (mixed uremic osteodystrophy)
 
Can produce "renal rickets" in children

49

Infection of bone

osteomyelitis

50

Primary vs secondary mode of acquisition 

•"Primary" mode of acquisition:  hematogenous spread to bone from often occult source elsewhere (more common in kids)
•"Secondary" mode of acquisition:  spread to bone from adjacent contiguous infection (joint infection/other soft tissue infection) - commonly diabetic ulcers w/ MRSA 

51

Direct infection mode 

e.g., compound fractures allowing direct injection of common bacteria onto raw fracture surfaces; orthopedic procedures ± prosthetic devices

52

Hematogenous subtype pyogenic/suppurative type osteomyelitis

Commonest in children/young adults
Favors long bones:  usually begins in metaphyseal region
Half the cases have no obvious "seeding" source of

  infection elsewhere in the body

Adults tend to have vertebral infection
Dx:  blood or direct bone culture (children may be culture negative)

53

Common pathogens osteomyelitis

Staphylococcus aureus (95% of cases without predisposing morbidity)
Streptococcus
Hemophilus influenzae (now uncommon)
Gram-negative bacilli
NOTE:  Patients with sickle-cell anemia tend to get salmonella osteomyelitis (worry w/ food posisoning)

54

Sxs osteomyelitis (common bacterial type)

Bone pain, erythema, swelling — fever/chills variable

 

Early infection (<10 days) often not detectable by routine x-ray

–bone scans/MRI scans better at early detection

55

Pathology Osteomyelitis 

Most infections begin in metaphyseal marrow space

Possibilities:

– Resolution of infection while still a small nidus

– Walled-off chronic infection (Brodie's abscess)

– Advanced infection: Subperiosteal and intramedullary spread, Death of bone (sequestrum), Periosteal new bone formation

56

Suppruative osteomyelitis longterm/chronic complications

Suppurative arthritis (adjacent joints)

Sinus tracks to skin

Growth disturbance (children)

Deformity

Amyloidosis (secondary seen in longterm inflammation)

57

Commonest causes of direct extension/injection osteomyelitis in adults 

–Compound fractures

–Contamination during orthopedic surgical procedures

–Extension from adjacent joint/soft tissue infection; diabetic vascular disease

–Causative bugs, Rx, and complications similar to hematogenous type

58

Treatment suppurative osteomyelitis

Need early/timely dx and tx to avoid chronic

Aggressive (usually I.V.) antibiotic therapy

± Surgical drainage/debridement

Occasionally amputation for chronic cases

59

Tuberculous Osteomyelitis (spread, location in body, severity, incidence)

•Usually 2° to hematogenous spread from lungs

•Prefers spine (Pott's disease) and long bones

•Highly destructive osteomyelitis with tendency to involve neighboring joints

•Relatively rare form of osteomyelitis in U.S.A. except in Third World immigrants and immunosuppressed patients

60

Fungal osteomyelitis common causes and spread 

•Blastomycosis (more here) and coccidioidomycosis (Southwest):

Commonest causes of fungal osteomyelitis in non-immunosuppressed patients

Almost always 2° to hematogenous spread from lungs; original pulmonary infection may have gone undiagnosed or be asymptomatic

 

Bacterial much more common

61

Syphilitic osteomyelitis

VERY RARE

Risk currently towards fetus

62

best way to diagnose osteomyelitis at early stage

MRI

63

Bone infarcts due to ________ of ____________ causations

Most common identifiable causes 

•Bone infarcts due to ischemia of varying/often poorly understood causations

Commonest identifiable causes are fractures, corticosteroid Rx, and alcoholism

64

Avascular Bone necrosis/infarction most commonly affects:

femoral head:

Can be 2° to subcapital fractures of femoral neck

Causes necrosis of bone with slippage of articular cartilage

65

Legg-Calve-Perthes disease

osteonecrosis of femoral head (? due to trauma), especially ages 4-8 (boys 5:1)

66

Avascular bone necrosis/infarction associations

Fractures, Legg-Calve-Perthers, Corticosteroid therapy, Alcoholism, Gaucher's ds, SLE, Sickle Cell anemia, Caisson's ds

67

Caisson's disease

The bends

Nitrogen comes out too fast - bones are kind of least of the worries

68

Subchondral infarcts

typically cause pain w/ activity

69

Medullary infarcts

usually clinically silent unless large (e.g., hemoglobinopathy, Caisson's disease)

70

Multiple infacts 

especially with chronic corticosteroid Rx

71

Complications of avascular bone necrosis/infarction

2° degenerative joint disease

Bone growth deformities (childhood)

Pathologic fracture

72

Paget's disease of bone (pearls)

(Osteitis deformans)

Elderly

Anglosaxon ancestry (strong family hx)

Elevated serum alkaline phosphatase

Deformed bone

73

Paget's - which bones and how many 

May involve multiple bones (polyostotic─most patients) or localized to a single bone (monostotic)

Prefers larger bones (skull, pelvis, tibia, femur, spine)

74

Paget's - focal acceleration of bone resoprtion followed by haphazard new bone formation

3 phases 

Lytic - inc. osteoclasts w/ bone resorption, inc vascularity

Mixed - inc. osteoclasts w/ inc osteoblasts, inc vascularity

Sclerotic - most characteristic radiologically (osteoblastic phase)

75

Paget's clinical/imaging featurse

•Most patients asymptomatic
•Widening / bowing of long bones
•Distorted / widened pelvic bones
•General weakening of affected bone causing increased fractures

76

Paget's sxs

•principally pain (due to fractures, compression of cranial or spinal nerve roots by foraminal encroachment, or secondary degenerative joint disease due to subchondral bone deformity).

•Sometimes skin overlying an affected bone is warm during lytic / vascular phase (high output CHF possible in polyostotic disease).

77

Radionuclide bone scan - Pagets

Sensitive for early phase ds

78

Paget's Widening of Bone

•Widening of bone favors Paget's disease over other pathology HALLMARK

X-ray features usually typical to experienced radiologist; occasionally may mimic malignant bone disease (need Bx)

79

Paget's Lab

serum alkaline phosphatase typical for active disease

–Suspect Paget’s biochemically if: Older patient, Isolated ­ alkaline phosphatase level, Normal serum calcium, No hepatobiliary disease

80

Complication w pagets

bone sarcoma, severe polyostotic ds

81

82

Cause of Pagets

Current theory: 
–Due to a latent viral infection of osteoclasts in a genetically susceptible person

83

Congenital bone disorders 

•Localized absence or duplication of a bone(s)

•Malformation of craniopsinal axis (spina bifida, meningomyelocele, meningoencephalocele)

•Achondroplasia

•Osteogenesis imperfecta

•Osteopetrosis

•Bone disease associated with mucopolysaccharidosis

84

Osteogenesis imperfecta

•Congenital disorders of type 1 collagen
Either qualitatively abnormal or quantitatively too little
Result:  insufficient / inadequate collagen for normal osteoid production --> risk of fractures

85

Osteogenesis imperfecta (variants)

Variable degrees of osteopenia/osteoporosis

Variable tendencies for fracture depending on genetic subtype

–Spectrum from type II variant, fatal in utero to type 1 variant with fracture tendency that lessens post-puberty

86

Tumors/Tumor-like lesions involving brain (Sxs)

•Whether primary or secondary (metastatic) type, symptoms often are nonspecific:

Pain and/or swelling

Pathologic fracture

87

Tumors of bone (Xray Features)

•valuable for predicting:

Along with age—likelihood of primary vs metastatic lesion

Ability to subtype primary bone tumors by location and x-ray character

Usually accurate in separating benign from malignant lesions

88

Bone tumors classified as:

osteolytic (demineralizing effect) - (i.e. myeloma)

osteoblastic (increased bone density relative to normal bone) (i.e. metastatic prostate cancer)

mixed osteolytic/osteoblastic features

89

Most common sources of metastatic tumor to skeleton

lung, breast, prostate

Almost every known malignancy is capable of metastasizing to bone

Larger bones usually perfered (but can be any)

90

_____________________ are the most common malignancies involving bone

Metastatic tumors to skeleton

91

Classical myeloma clinical presentation 

Multifocal osteolytic lesions with bone pain

Often associated hypercalcemia

Fractures common

92

Plastocytoma of bone

•localized tumor of plasma cells—eventually tends to evolve towards classic myeloma

93

Hemic malginancies affecting bone

Classic myeloma

plasmacytoma of bone

lymphoma

leukemia

94

Lymphoma

Most non-Hodgkin's lymphomas involve bone at some time during their course

May cause sufficient focal tumefaction to compromise bone strength ® pathological fracture

Rarely can see 1° lymphoma of bone

95

Leukemia

By definition, always affects bone marrow

Clinically can produce diffuse/multifocal bone or joint pain (especially ALL in children)

May produce skeletal changes 2° to expanded marrow spaces

Occasionally can produce localized tumefaction of bone

96

Osteoblastic hallmark for

prostate cancers in males

97

Osteolytic hallmark for

myeloma

 

98

Primary bone tumors mostly arise in _______ (location) and ________ (population)

Metaphyses of long bone

Kids

99

Most common primary benign tumors 

–Osteochondroma

–Giant cell tumor

–Chondroma

–Osteoid osteoma

–Fibroma (metaphyseal fibrous defect)**

100

Most common malignant primary tumors 

Osteogenic sarcoma (osteosarcoma) - BAD, most common in kids

Chondrosarcoma - most common in adults

Lymphoma 

Ewing's sarcoma - one of most aggressive 

Chordoma - bottom or top of spine 

 

**Again, children

101

Osteosarcoma vs chondrosarcoma

•Osteosarcoma is the commonest primary malignant tumor of children/young adults

•Chondrosarcoma is the commonest primary malignant tumor of middle-aged/older adults

102

Benign vs malignant preference for location w/ primary bone tumors

•Most benign cartilage tumors (chondromas) tend to involve the small bones (hands and feet)

•Most malignant cartilage tumors (chondrosarcomas) tend to involve the larger bones (long bones, pelvis, ribs, spine)

103

Sarcomas tend to spread via ______

hematogenous route (rather than lymph nodes like carcinoma), ie. go to lungs

104

Tx primary bone tumor cancers 

Aggressive

surgery, chemo, and/or radiation 

105

Giant Cell Tumors 

Primary bone tumor

•"intermediate" between benign and malignant states

•50% recur following simple curettage

can be locally aggressive

•Some can metastasize to lungs

106

Metaphyseal fibrous defect 

•Fibroma, fibrous cortical defect

•Commonest bone lesion

•Regarded as a non-neoplastic developmental defect

•Can be found in one-third of children

•Often regress spontaneously

•Occasionally are large enough to compromise bone strength/cause pathological fracture

107

Conditions taht may simulate primary/metastaic bone tumors

•Osteomyelitis

•Paget’s disease

•Hyperparathyroidism

•Fibrous dysplasia

•Exuberant callus (healing fracture site)

•Avulsion fractures

•Assorted benign cysts

•Histiocytosis X

•Bone infarcts

•Mast cell disease

•Giant cell reparative granuloma

108

tx osteosarcoma

Pre-op tx  and amputation

109

Most common primary malignant bone tumor of adolescents/young adults

Osteogenic sarcoma

110

Osteosarcoma sxs

pain, pathologic fracture

111

Osteosarcoma favors _________ (location)

•metaphyseal regions of large long bones (esp. knee)

112

Variants osteosarcoma

common high-grade / aggressive types (grade 3-4)

–40% mortality rate

ulow-grade types

–curable by adequate surgical excision alone

113

Tx failurs of osteosarcoma associated w/ 

local recurrence and pulmonary/other metastases

114

Osteosarcoma may be secondary to 

Paget's, prior irradiation, old bone infarcts (link to retinoblastoma gene mutations?)

115

______ bone osteosarcoma more curable

jaw

116

Commonest primary bone tumor of middle-aged/older adults

swelling, pain

117

Chondrosarcoma sxs

swelling, pain

118

chondrosarcoma prefers _______ bones

larger long bones, central skeleton

especially pelvis, rare in small bones

119

Chondrosarcoma may grow to _________ before dx 

very large size (especially pelvis)

usually typical xray features (hallmark)

120

Multiple variants chondrosarcoma

Most common are low-grade tumors with slow growth and delayed risk of metastasis

Xray features to differentiate 

121

Chondrosarcoma tx

adequate surgical excision (can be very late metastasis)

122

Most aggressive/lethal of all primary bone tumors

Ewing's sarcoma

123

Ewing's sarcoma usually affects ________ and prefers _______ bone

•Usually affects a younger age group than osteogenic sarcoma (esp. peripubertal ages)

•Prefers diaphysis of long bones & flat bones of pelvis

124

Diff Dx Ewing's Sarcoma

•Some patients: The x-ray features with fever & leukocytosis may mimic osteomyelitis

125

Histology EWing's sarcoma

Composed of small, morphologically undifferentiated tumor cells now known to be primitive neuroectodermal neoplasm (PNET)

–Usually t(11;22)

–Resembling leukemia, lymphoma, neuroblastoma, Wilm’s tumor, small cell Ca

126