1
Q
Principle of open incisional biopsy
A
Incision: longitudinal incision for extension of incision for definitive management
Approach: don’t expose NV structures*
All tissue exposed during Bx = contaminated*
Biopsy: THROUGH INVOLVED COMPARTMENT***
Closure: if using drain, keep in line with incision to allow drain site to be removed w/ definitive surgical extensile incision***
2
Q
Distal femur likely osteosarcoma –> which compartment to biopsy through?
A
Can biopsy through either anterior or lateral INTRAmuscular approach –> will resect at time of final operation
3
Q
What does chemo induce in cancer cells?
Tyrosine kinase inhibitor?
Good prognostic sign for necrosis with chemo?
What ortho tumors need chemo?
A
Chemo induces APOPTOSIS***
Chemo may target specific proteins over expressed in cancer cells, ie tyrosine kinase inhibitors:
Imatinib (Gleevec) for CML
Geftinib/EGFR inhibitor for lung and breast
Ertlotinbi for NSCLC and pancreatic
Good prognostic = >98% necrosis with chemo**
Ortho tumors requiring chemo: Osteosarcoma*** Ewings*** MFH*** Dediff chondrosarc
4
Q
issue with doxorubicin?
A
Cardiac toxicity*** –> CHF/caridomyopathy
use Dexrazoxane*** to mitigate toxicity
5
Q
Mirel Criteria
A
Site
UE = 1
LE = 2
Peritroch = 3
Pain
Mild = 1
Moderate = 2
Severe/functional = 3
Lesion
Blastic = 1
Mixed = 2
Lytic = 3
Size
<1/3 = 1
1/3-2/3 = 2
> 2/3 = 3
Score >/= to 8 –> prophylactic fixation***
If lower than this consider XRT***
6
Q
What type of bony met has the worst prog?
A
Lung cancer and melanoma***
7
Q
Enneking/MSTS staging system
A
One for malignant and one for benign lesions
Malignant = defined by Roman numerals (I, II, III)
Osteosarc most commonly stage IIB***
Benign = Arabic numerals (1, 2, 3) 1= latent lesion, enchondroma or NOF 2= active lesion, ABC/UBC, chondroblastoma, GCT 3= aggressive lesion, GCT (some)
Stage IA = low grade, T1/intracompartmental (bone tumor confined within cortex***)/ no mets
Stage IIB = low grade, T2/extracompartmental (bone tumor extends beyond cortex)/no mets
Stage IIA: High grade, T1/intracompratmental/no mets
Stage IIB: High grade, T2/extracompartmental/no mets
Stage III = mets
8
Q
Where will osteoid osteoma be in spine?
Why are osteoid osteomas painful?
Size?
Histology?
A
Posterior elements***
Concavity of scoliosis***
Pain 2/2 PROSTAGLANDIN E2*** and Cox 1 and 2 expression –> pain relieved by NSAIDs
Size generally <1.5 cm –> otherwise think osteoblastoma***
Histo: distinct demarcation between nidus and reactive bone*
Nidus: immature osteoid/woven bone with sharp border of osteoblastic rimming
Uniform plump osteoblasts have regularly shaped nuclei w/ abundant cytoplasm (indicating benign lesion)*
9
Q
Where to NOT perform RF ablation for osteoid osteoma?
A
Spine (neural elements close)
Fingers (thermal necrosis to overlying skin and NV elements)
10
Q
What is most common malignancy of bone?
Primary malignancy of bone?
Primary sarcoma of bone?
A
Most common overall: mets
Most common primary malignancy of bone: multiple myeloma
Most common primary sarcoma of bone: intramedullary osteosarcoma
11
Q
Intramedullary osteosarcoma
Where does occur in skeleton?
Where does metastasize to?
What stage present at most commonly?
Genetics?
Long term survival?
A
Occurs in distal femur and prox tibia most commonly***
Also in humerus, proximal femur and pelvis
Mets: lung most common, bone 2nd most common
Stage presents at: stage IIB most commonly (10-20% stage III with lung mets**)
Genetics: Rb carriers are at risk of osteosarcoma
Risk increased with ROTHMUND THOMSON syndorome (poikioderma rash, absent eyelashes, hair)
Prog: 75% long term survival
Worse prognosis with: Advanced stage of dz (most predictive)*** Response to chemo High serum alk phosphatase*** high LDH***
12
Q
Treatment for osteosarcoma?
A
Multi-agent chem and limb salvage***
Chemo for 8-12 wks preop and then 6-12 months postop
Wide surgical resection only –> low grade osteosarcoma such as PAROSTEAL osteosarcoma
13
Q
Parosteal osteosarcoma
Where?
Grade?
Prognosis?
Histo?
Tx?
A
Posterior distal femur, proximal tibia, and proximal humerus (80% occur in femur)**
Low grade osteosarcoma***
Prognosis –> 95% long term survival
Dedifferential is poor pronsijoc factor
Invasion into medullary cavity does NOT AFFECT LONG TERM SURVIVAL***
Histo: Low grade
High rate of MDM2 amplification* and ring chromosomes*
Tx: wide local surgical excision*
Chemo NOT indicated unless high grade
14
Q
Periosteal osteosarcoma
Grade?
where?
Genetics?
Prog?
Imaging?
Tx?
A
Grade: intermediate surface osteosarcoma
Where: diaphysis of long bones (femur and tibia most common)
Genetics: mutation of p53 in 15-20%*
Ass’d with Li-Fraumeni syndrome
Prog: 20-35% chance of pulmonary mets***
Intermediate prog between parosteal and intramedullary osteosarcoma
Imaging: classic “sunburst” or “hair on end” periosteal reaction ***
Tx: same as intramedullary osteosarcoma (chemo-surgery-chemo)
15
Q
What is most common bone tumor of hand?
A
Enchondroma***
16
Q
Ollier’s dz?
A
Skeletal dysplasia w/ failure of normal endochondral ossification
Enchondromas throughout the metaphyses and diaphyses of long bones
Risk of malignant transformation = 30%***
17
Q
Mafucci’s syndrome?
A
Multiple enchondromas AND soft tissue angiomas***
enchondromas markedly expand the bone and angiomas seen as small, round calcified phleboliths***
Risk of malignant transformation = 100%***
Also risk of visceral malignancies (GI etc)**
18
Q
Tx for enchondromas?
A
Observation –> tx for vast majority***
Serial XR at 6 mo and 12 mo to confirm no change
Intralesional curettage and bone grafting
For lesions that change on serial XR
Symptomatic lesions
Path fx –> IMMEDIATE curettage and grafting
19
Q
Osteoblastoma
Size?
Where?
Ass’d condition?
Sx?
Tx?
A
Size: Nidus >2 cm***
Where: Most common in posterior elements of spine* (50% spine lesions have neuro sx*)
Ass’d condition: Secondary ABC in 10-40%**
Sx: pain, not relieved with NSAIDs
50% lesions in spine have neuro sx***
Tx: Operative, curettage or marginal excision w/ bone grafting*
Recurrence 10-20%
20
Q
Chondroblastoma - where?
Metastatic potential?
Sx?
XR?
Histo?
Tx?
A
Epiphyseal lesion in young patient (usually <12 y/o)*
Proximal tibia»>proximal humerus etc
Usually epiphyseal, but CAN CROSS PHYSIS*
Metastatic: <1% develop benign pulmonary mets (similar to GCT)**
Sx: Progressive pain at tumor site
XR: Well circumscribed EPIPHYSEAL LYTIC lesion***
Sharply demarcated, may cross to metaphysis
Cortical expansion may be present
Marrow edema (like osteoid osteoma) on advanced imaging***
GET CHEST XR*** (benign pulmonary mets, like GCT)
Histo: Chondroblasts arranged in “Chickenwire” or “cobblestone” pattern
1/3 have secondary ABC
Tx: Extended intralesional curettage and bone grafting***
21
Q
Multiple hereditary exostosis (MHE) –> where is pathology?
Inheritance?
Mutation?
Which mutation is most severe?
Chance of malignancy?
A
Mutations affect eh PREHYPERTROPHIC CHONDROCYTES of physis***
Inheritance: Autosomal dominant
Mutation: EXT1, EXT2, EXT3 (tumor suppressor genes)*
Leads to DECREASED production of HEPARIN SULFATE by chondrocytes found at physis*
Most severe: EXT1 mutations*** more likely to get chondrosarcoma, more exostoses
Chance of malignancy: 5-10% Chance of transformation to chondrosarcoma***
Higher chance of chondrosarcoma in adults if carriage cap >2cm***
22
Q
Limb deformities in MHE?
A
Most common in knee, forearm, ankle
Femoral shortening and LLD**
Coxa valga
Knee valgus* (shortened fibula and patellar dislocation)
Ankle valgus* (shortened fibula)
UE
Ulnar shortening*
Radial bowing and radial head dislocation*
Ulnar shortening and ulnar deviation of hand***
23
Q
Prognosis for chondrosarcoma?
A
Histo grade correlates w/ survival
Gr I: 90% 5 year survival
Gr II: 60-75%
Gr III: 30-50%
De-diff: <10%
Increased TELOMERASE ACTIVITY –> determined by reverse transcriptase PCR shown to directly correlate with RATE OF RECURRENCE***
Get chest CT**
24
Q
Multiple myeloma
what types of chains produced?
Labs?
A
Neoplastic plasma cells produce immunoglobulins:
Heavy chains: IgG (52%)***, IgA (21%), IgM (12%)
Light chains: kappa and lambda
AKA Bence Jones protein
Labs:
Anemia*
Elevated Cr*
Hyper Ca* –> excessive bone respiration
SPEP* –> M spike present*** (50% IgG, 25% IgA)
Beta-2 microglobulin –> marker of dz severity/prognosis
Urine: UPEP –> shows BENCE JONES PROTEIN –> secreted immunoglobulin kappa and lambda light chains***
25
What causes punched out lesions of multiple myeloma?
Osteoclastic bone respiration via:
RANKL*** (RANKL acts on osteoclastic cells***, not neoplastic cells)
IL6***
MIP-1 alpha***
26
Immunhistochemical stain for MM?
CD138+
27
How to distinguish MM from solitary plasmacytoma?
Bone marrow aspirate***
Solitary plasmacytoma --> 10-30% plasma cells
MM: 30%+ plasma cells***
28
Tx MM?
Nonop vs op?
Painful VCF?
External beam radiation only --> solitary plasmacytoma*** (45-50 Gy)
Multiagent chemo +/- stem cell transplant +/- bisphosphonates --> MM***
Operative:
Surgical stabilization and XRT*** --> complete or impending Fx, life expectancy >3 months
Painful VCF: kyphoplasty***
29
How to diagnose lymphoma?
Histo?
How to differentiate from other similar tumors on histo?
Tx?
Bone marrow biopsy
Histo: Mixed small round blue cells (different sizes and shapes)
To differentiate form other small round blue cell tumors: CD99 NEGATIVE and absent 11:22 translocation***
CD20 and CD45 positive****
Tx: multi agent chem +/- XRT
Fx stabilization
30
What is the mutation of fibrodysplasia ossificans progressiva?
FOP/ "Stone man disease"***
Progressive HO and congenital malformation of great toe***
Hallux deformities help distinguish from MHE as well as bridging ossification***
Mutation of ACVR1 gene***
Activin A type I receptor --> a BMP type 1 receptor***
31
Myositis ossificans vs osteosarcoma imaging?
Myositis ossificans --> well defined ossified rim, maturing PERIPHERALLY more than centrally***
Osteosarcoma does the opposite --> matures centrally***
32
Tumoral calcinosis --> where?
Pathophys?
Differntial?
Tx?
Occurs most commonly around HIP (Troch bursa = most common) > shoulder***
Pathophys: unknown but inborn abnormality of PHOSPHORUS metabolism implicated
FGF-23 defect*** --> familiar hyperphosphatemic tumoral calcinosis***
Differential:
Calcinosis of renal failure --> no rad/histo differences
Dx based on Vit d lvl, GFR, hyperphosphatemia, hx of renal failure
Synovial osteochondromatosis***
Occurs WITHIN joint/tendon sheath/intra articular (makes different from tumoral calcinosis)**
Tx: observation vs complete excision (only for symptomatic cases)
33
Giant cell tumor --> where?
Ass'd conditions?
Imaging?
Benign aggressive tumor found in METAPHYSIS of long bones, often around knee in young adults
Distal femur> proximal tibia > distal radius > sacral ala
10% in spine w/ sacral ala most common in axial skeleton***
In spine, will occur in vertebral body***
Phalanges of hand also common***
Ass'd condition: MALIGNANCY***
mets to lungs in 2-4% (wrist and hand most likely to be metastatic***)
Imaging: XR of extremity and CXR/chest CT*** (lung mets)
Eccentric lytic epiphyseal/metaphyseal lesion
34
Cell types in GCT?
Type I: mononuclear stromal cello hat resembles interstitial fibroblasts --> this is the neoplastic/tumor cell***
Type II: from monocyte/mcacrophage family --> precursors of giant cells
Type III --> giant cells w/ many nuclei (up to 50)
characteristics similar to OSTEOCLASTS*** --> resorb bone***
Cells have enzymes (TRAP, carbonic anhydrase II, cathepsin K)***
Can have secondary ABC
Type II and III cells have IGF 1 and IGF II activity
RANK pathway = important ***
Use DENOSUMAB to act on this pathway***
35
Tx of GCT?
Nonop
Radiation only --> ONLY for inoperable of multiply recurrent lesions --> up to 15% malignant transformation
Medical management
To stabilize lesions
Excellent response with DENOSUMAB***
Operative
Extensive curettage, adjuvant Tx and recon***
20-40% recurrence w/ curettage and grafting alone vs 3-10% with adjuvant tx (phenol, cry, argon beam, high speed burr)
Complete resection and recon --> vertebral body
Amputation: hand lesions w/ cortical breakthrough not amendable to intercalary resection***
36
How does denosumab work?
HUMAN MONOCLONAL ANTIBODY that targets RANKL
RANKL also known as Nuclear factor kappa-B ligand***
Vs osteorotegrin = DECOY receptor for RANKL
37
Ewing's sarcoma --> where?
Genetics?
Prognosis?
Imaging?
How to rule out mets?
Where: 50% in DIAPHYSIS of long bones
Most common locations: pelvis, distal femur, proximal tibia, femoral diaphysis, proximal humerus***
Genetics: t(11:22) translocation --> EWS-FLI1 ***
11:22 useful to differentiate from other round cell lesions***
Prognosis --> METS are most important
Lung mets better prognosis than bone/bone marrow mets***
Imaging
Destructive lesion in diaphysis or metaphysis w/ moth eaten appearance
Periosteal reaction = "onion skin" or "sunburst" appearance***
Chest CT to work up for mets
also MUST get a BONE MARROW BIOPSY to rule out mets***
38
Histo for Ewings?
Immunstaining?
Differential?
Grossly --> liquid consistency mimicking pus
Histo: sheets of small round blue cells
Pseudo rosettes --> circle of cells w/ necrosis in center
```
Immunstaining:
CD 99 positive***
CD34 negative*** (vs lymphoma = CD 34 positive and CD 99 negative)***
Vimentin
PAS positive (intracellular glycogen)**
```
```
Differential: small round cell by age
<5 = neuroblastoma or leukemia
5-10: eosinophilic granuloma
5-30: Ewings***
>30 = Lymphoma
>50: myeloma
```
39
Tx of Ewings?
Nonop: Chemo + rads/XRT
Nonresectable in spine
Trend towards resection and away from XRT --> risk of secondary malignancies**
Operative: chemo + limb salvage +/- adjuvant XRT
Chemo: vincristine, doxorubicin, cyclophosphamide and dactinomycin**
Preop chemo for 8-12 wks, surgical resection, adjuvant chemo for 6-12 months (same as osteosarcoma***)
Adjuvant XRT: not necessary if margins are adequate and good response to chemo
40
What is second most common bone sarcoma?
Ewing's ***
second after osteosarcoma**
41
Translocations:
t(9:22)?
t(11:22)?
t(12:16)?
t(x:18)?
t(12;22)
t(9:22) = chondrosarcoma; EWS-CHN
t(11:22) = Ewings; EWS-FLI1
t(12:16) = myxoid liposarcoma; TLS-CHOP
t(x:18) = Synovial sarcoma; SYT-SSX1
t(12;22) = clear cell sarcoma; EWS-ATF1
42
Adamantinoma --> where?
Ass'd condition?
Prognosis?
Sx?
imaging?
Histo?
Tx?
Low grade malignant tumor of unknown etiology --> always in MID-TIBIA
Ass'd condition: osteofibrous dysplasia
(Adamantinoma patients generally OLDER)***
Prog: may met to lungs (25%)***
Recurrence is uncommon w/ negative margin excision
sx: pain for months-years
Bowing deformity or palpable mass of tibia***
Imaging: Mult sharply circumscribed Lucent lesions/ soap bubble appearance
Histo: BIPHASIC --> epithelial and fibrous mesenchymal cells***
Nests of epithelial cells arranged in palisading glandular patter on background of fibrous storm***
Tx: Wide resection
43
Non ossifying fibroma (NOF)
Imaging
Histo?
Tx?
Ass'd condition?
imaging: DIAGNOSTIC***
metaphyseal eccentric "bubbly" lytic lesion w/ sclerotic rim, may thin cortex, length > width
As bone grows lesion migrates to diaphysis and enlarges, then become sclerotic
Histo: Fibroblastic spindle cells in WHIRELD parttern
Numerous giant cells
Hemosiderin
Occasional ABC
Tx: observation (will spontaneously resolve and reossify in 2nd and 3rd dead)
Fx: cast
May treat operatively if large and symptomatic (>50-75% cortical involvement
Ass'd condition: Jaffe-Campanacci syndrome (care au last spots, MR, cardiac abnormalities, eye and gonad abnormalities)
44
Malignant Fibrous Histiocytoma/Plemorphic Sarcoma --> where?
Risk factor?
Genetics?
Prognosis?
Imaging?
Histo?
Metaphysis of long bones
Risk factor: 25% arise as SECONDARY LESION from bone infract, Pagets, or prior radiation**
Genetics: mutations in p53
Prognosis: 50-60% at 5 years, pulmonary mets in up to 30%***
Imaging: lytic and destructive lesion in metaphysis
Histo: Pleomorphic spindle cells and histioctytic cells is storiform pattern***
Malignant giant cells with grooved or indented nuclei
Tx: Neoadjuvant chemo, wide resection, postop chemo (same as osteosarcoma, Ewings etc)***
45
Chordoma --> where?
Prognosis?
sx?
Imaging?
Histo?
how to differentiate from chondrosarcoma?
Tx?
Malignant tumor of PRIMITIVE NOTOCHORDAL ORIGIN***
Where: most common primary malignant spinal tumor in adults
50% in sacrum and coccyx***
35% in sphenoid-occipital region
10% in mobile spine
Prognosis: Mets in 30-50%***
60-% 5 year, 25% long term
Sx: Insidious onset of pain, may have bowel or bladder changes
Motor deficits are RARE due to most lesions distal to S1***
More than 50% sacral chordomas are palpable on rectal
Imaging: CT shows midline bone destruction and sot tissue mass
Bright on T2
Histo: Foamy, vacuolated, physaliferous cells
To distinguish from chondrosarcoma: KERATIN POSITIVE***
Tx: Rads vs wide margin resection
46
ABC --> where?
Genetics?
Imaging?
Histo?
tx?
Benign lesion which can be locally destructive
Location: 15% in spine** (posterior elements)**
>60% in long bones***, usually in metaphysis
Metatarsal and calc are most common locations in foot***
Genetics: upregulation of UBIQUTIN-SPECEIFIC PROTEAS (USP6)***
Imaging: expansile, eccentric and lytic lesion w/ bony septa ("bubbly appearance")***
Metaphysis**
MRI: multiple fluid lines***
Histo: Blood filled spaces WITHOUT endothelial lining***
Tx: none fx management --> ABC with ACUTE FRACTURE***
Once healed, tx as ABC w/o fx unless spontaneous healing of ABC
Operative
Aggressive curettage +/- adjuvant and bone grafting
For symptomatic ABC WITHOUT fracture***
Local recurrence in up to 25%, most common in kids with open physis**
47
Unicameral Bone Cyst/UBC --> where?
Prognosis?
Phases?
Imaging?
Usually found in proximal humerus in young patient***
Can be other areas such as prox femur, distal tibia, ilium, calcareous, distal radius etc
Prog: As pt approches skeletal maturity, UBC will decrease in size and may heal after growth complete***
Requires close f/u while in active phase due to recurrence and risk of Fx and growth arrest***
Phases: active --> cyst adjacent to physis***
Latent: normal bone separates cyst from physis**
Imaging: Central, lytic, well demarcated metpahyseal lesion (2-3% may cross phsysis***)
Symmetric thinning of cortices
"fallen leaf" = path fx w/ fallen cortical fragment in base of empty cyst*-**
Histo: Cyst with thin fibrous lining, giant cells, hemosiderin
Tx: Immobilization alone: proximal humerus w/ path fx (15% heal with native bone)
Aspiration/methylpred injxn
Active cysts***
Operative: curettage and bone grafting +/- internal fixation
Symptomatic latent cyst that dont' respond to steroid injection
Cyst at risk for fx
Proximal femoral lesions w/ path fx have high rate of refractor and malunion --> internal fixation****
contraindications of ORIF: Active lesions communicating with physis --> growth arrest***
48
Fibrous dysplasia: what is it?
Where?
Genetics?
Ass'd condition?
Imaging?
Developmental abnormality caused by failure of production of normal lamellar bone --> poorly mineralized trabeculae
Location: any bone, proximal femur is most common***, followed by rib, maxilla, tibia
Genetics: GNAS mutation****
Gs alpha ACTIVATING mutation --> increased cAMP***
Ass'd: McCune Albright
Cafe au last spots/coast of Maine pattern, precocious puberty, renal phosphate wasting due to FGF-23 (oncogenic osteomalacia), fibrous dysplasia --> get AP spine to r/o scoliosis***
Mazabraud syndrome: polyostotic fibrous dysplasia, soft tissue intramuscular myxomas**
Prognosis: 1% risk of malignant transformation to osteosarcoma, fibrosarcoma or MFH***
Imaging: Ground glass lesion, Shepherd's crook deformity***
AP spine for scoliosis**
Histo: Alphabet soup/chinese letters; fibroblast proliferation surrounding islands of WOVEN BONE***
Woven bone lacks ostoblastic rimming (seen in osteofibrous dysplasia***)
Tx: nonop, bisphosphonates for symptomatic pts to decrease pain/bone turnover
ORIF: Areas of high stress (femoral neck), NEVER use autograft, quickly goes to fibrous dysplasia
Coxa vara: intertroch osteotomy***
49
Where does HO occur after brain injury and when?
Within 2 months of neuro injury (brain or spinal cord)***
TBI: Hip***>elbow>shoulder>knee
-Elbow more common following brain trauma
Spinal cord injury: Hip***>knee>elbow>shoulder
50
Treatment for HO?
Prophylaxis: Indomethacin = 75 mg/day for 10 days - 6 wks
Perioperative XRT: 700 cGy 4 hours preop or within 72 hours postop**** (<550 cGy not effective)
Resection: loss of ROM and function
Timing: marked decrease in bone scan activity*** AND normalization of ALP***
6 months for general trauma, 12 months for SCI, 18 months for TBI
51
Risk factors for HO?
TBI
SCI
Amputation through zone of injury in blast injury patients
Severe burns
Prolonged ventilator time in multiply traumatized patients
52
Paget dz --> pathophys?
Abnormal bone remodeling --> original osseous tissue reconstructed through active interplay between excessive bone respiration and abnormal new bone formation
INCREASED OSTEOCLAST ACTIVITY*** --> virus mediated***
Ass'd condition: Paget sarcoma*** --> osteosarcoma > fibrosarcoma and chondrosarcoma, <10% survival, Tx w/ chemo and surgery***
Lab: Elevated ALP, elevated urinary collagen cross links, urinary HYDROXYPROLINE***, increased N-telopeptide, C-teloptptide, NORMAL CALCIUM***
\Tx: Observation
Medical tx aimed at osteoclast inhibition --> bisphosphonates*** (1st line), 2nd line = calcitonin***
Teraperitide CONTRAINDICATED due to risk of osteosarcoma***
THA: higher risk of bleeding, anterior dislocation***
TKA: Malalignment***
53
Paget dz plate vs nail?
Use plate with metaphyseal osteotomy to fix angular deformities, higher union and quicker union than nail or diaphyseal ostetotomy
54
Osteofibrous dysplasia histo?
Tx?
Similar to fibrous dysplasia EXCEPT has osteoblastic rimming present***
Fibroblast proliferation surrounding islands of woven bone w/ osteoblastic riming
Tx: Observation = 1st line***
Bracing: if deformity significant and interfering w/ walking
Operative: deformity correction w/ osteotomy: rarely needed, do after skeletal maturity
55
What is Hans Schuller Christan dz?
Triad of:
Multiple lytic lesions***
diabetes insipidus***
Exopthalmos***
Diffiuse or nonspecific abdominal or chest pain
Langerhans cell histiocytosis w/ visceral involvement***
56
What to think about with histo with monocular cells with eosinophilic cytoplasm/ with prominent nuclear groove?
Tx of lesions?
Langerhans cell histiocytosis***
Tx: eosinophilic granulomas will have focal destructive lesions in young patients, often appear very aggressive but will heal spontaneously***
chemo only in disseminated form of histiocytosis**
57
Most common carcinomas to spread to bone?
Where do they met to in bone?
```
Breast***
Lung***
Thyroid***
Renal***
Prostate***
```
Most common sites of spread:
Thoracic spine***>proximal femur>humerus
Bartons' vertebral plexus: valveless venous system of spine that provides route for mets from organs to axial structures***
58
Pathophys of osteolytic metastatic bone lesions?
Osteoblastic?
Osteolytic: Tumor induced activation of osteoclasts***
Through RNAKL pathway
PTHrP positive breast Ca can activate RANKL production by osteoblasts***
IL-6, IL-11, PTHrP, TGF-beta***
Osteoblastic:
Tumor secreted endothelin 1****
Stimulates osteoblasts by decreasing WNT suppressor DKK-1 --> activates WNT pathway --> increases osteoblast activity****
59
Principles of metastasis/mechanism
1: Tumor cell intravasation***
E cadherin*** on tumor cells modulates RELEASE from primary tumor into bloodstream
PDGF ** --> promotes tumor migration
2: Avoidance of immune surveillance
3: Targe tissue localisation**
Chemokine ligand 12 in stromal cells bone marrow acts as homing chemokine for certain tumor cells and promotes targeting of bone
Tumor cell attaches to organ endothelial layer via INTEGRIN (expressed on tumor cell)
4: Extravastion into target tissue
Uses MMPs*** to invade basement membrane
5: Induction of angiogenesis**
Via VEGF***
60
Which two types of mets will bone scan be negative/cold so should get a skeletal survey?
Myeloma and thyroid carcinoma***
61
What to think about with metastatic lesions distal to elbow and knee?
LUNG***
Renal***
62
Which type of met does better with complete resection of lesion in terms of long term survival?
Renal cell carcinoma***
3 reasons:
Lower revision***
Increased patient survival***
Decreased overall complication rate vs IMN through lesion***
63
Which metastatic tumors do NOT respond well to XRT?
Renal***
Thyroid***
64
Worst survival rates for metastatic lesion?
Lung < renal < breast < prostate < thyroid***
65
Tokuhashi score specific for mets to spine?
Prognostic score based on 6 elements: general condition, estraspinal bony mets, number of vertebral bodies w/ mets, visceral mets, primary tumor, neuro compromise
Scores:
0-8: < 6months survival***
9-12: >6 months***
>12: >1 year***
66
Spinal instability neoplastic score?
SINS***
0-6 = No surgical consultation required
7-18 = surgical consultation advisable***
67
Bisphosphonate tx in metastatic lesions
Decreases skeletal related events by 30-40%***
Pain improvement in 50%***
Osteonecrosis of jaw in 2.5%
68
Which soft tissue tumors spread to lymph nodes?
RACES***
```
Rhabdomyosarcoma
Alveolar
Clear cell
Epithelioid
Synovial
```
69
What is standard XRT dose for soft tissue sarcoma?
50 Gy preop***
66 Gy postop***
Preop XRT = 30% wound complication
Postop: greater XRT induced morbidity and increased risk of radiation induced sarcoma
30 Gy used for met bone lesion***
70
PVNS - where?
Genetics
Imaging?
Histo?
Tx?
Knee > hip > ankle > shoulder > elbow***
Genetics: increased expression of CSF1 gene***
Imaging: low intensity on both T1 and T2 due to hemosiderin deposits***
Histo: Highly vascular w/ hyperlastic synovial cells
Hemosiderin stained mulinucleated giant cells***
Tx: total synevectoy*** (marginal excision)
External beam irradiation
When combined w/ synevectomy, reduces recurrence to 10-20% (from 30% with synevectomy alone***)
71
Treatment for localized PVNS?
Resection of nodule ONLY***
disseminated PVNS: complete synevectomy***
72
What is most common sarcoma of foot?
Synovial sarcoma***
73
Synovial sarcoma --> where?
translocation/fusion protein?
Histo?
Immunostaining?
Tx?
Most common sarcoma of foot***
t(X;18) SYT-SSX1, 2***
SSX2 = better survival***
SSX1 more common, larger tumor, more lethal
Histo: BIPHASIC
Spindle cells*** --> fibrous type of cells, small and uniform and found in sheets of malignant appearing cells w/ minimal cytoplasm and dark atypical nuclei***
Epithelial cells***
Gland, nest or cyst like cells
Immunostaining***
Vimentin***
Keratin** (epithelial cells)
Epithelial membrane antigen***
Tx: wide surgical excision + XRT
74
Which malignant soft tissue sarcoma often has calcifications on CT or XR?
Synovial sarcoma***
75
What to think when patient has multiple interarticular clarified lesions?
Synovial chondromatosis***
No calcifications in PVNS**
76
How to determine benign neurofibromas from malignant peripheral nerve sheath tumor?
PET-CT***
77
What is most common sarcoma in children?
Rhabdomyosarcoma***
Poorly differentiated round cells on histo**
Tx: Wide resection, chemo, XRT*** (chemo for kids)**
78
Translocation of Rhabdomyosarcoma?
t(2;13)***
Pax3-FKHR fusion protein***
79
Spindle cell lipoma...stains?
Tx?
Stains positive for CD34 but negative for S-100***
Tx with MARGINAL EXCISION***
80
What are Desmoid tumors ass'd with?
Histo?
Familial adenomatous polyposis**** (FAP)
FAP often has APC gene mutation***
Histo: well differentiated fibroblasts***
Stain 100% positive for estrogen receptor-beta***
Tx: Low dose chem only/TAMOXIFEN****
-inoperable lesions
Wide surgical resection + XRT
Symptomatic or recurrent lesion
81
What is a glomus tumor?
Tumor of the glomus body = perivascular temperature regulating structure located at tip of digit or beneath nail
May be called PARAGANGLIOMA***
May involve soft tissue AND/OR bone***
Sx: often have COLD INTOLERANCE, often painful***
Histo: Gland like or nest structures, separated by storm elements
82
What gene is amplified in well differentiated liposarcomas?
Myxoid liposarcoma translocation?
Well differentiated vs high grade liposarcomas on MRI?
Well differentiated: amplification of MDM2***
Also test for CDK4***
Myxoid liposarcoma: t(12;16)***/CHOP-TLS***
Well differentiated: bright on T1***, dark on T2 (like fat)***
vs high grade: like other sarcomas --> dark on T1, bright on T2***
83
Where do myxoid liposarcomas metastasize to?
Often to areas outside of lung, especially RETROPERITONEUM*** --> get CT chest/abdomen/pelvis***
84
Intramuscular myxoid on MRI?
Super bright on T2 (brighter than fat) vs lipoma = fat***
Super dark on T1 (darker than muscle) vs lipoma which will stay same as fat***
85
How to define toughness? on a graph?
Amount of Energy per volume a material can absorb before failure/fx***
Graph: area under stress/strain curve***
86
For longitudinal strain in cortical bone, how does elastic modulus and ultimate strength change?
Both elastic modulus and ultimate strength INCREASE as strain rate increases***
87
Most common failure for modular revision hip stem?
Fretting fatigue*** --> contacting components experience cyclic loads while small oscillatory motion occurs between them --> small flaws --> crack propagation***
88
Another term for ultimate strength?
Tensile strength*** --> maximum stress a material can withstand before breaking***
89
Elastic vs plastic deformation?
Elastic: change in length of material under load that RETURNS TO ORIGINAL LENGTH when load removed***
Plastic: Change in length that does NOT RETURN TO ORIGINAL after load removed***
90
Why place plate on the tension side of bone?
When plate on tension side, fracture will tend to close when bone is loaded, so that axial and bending loads are transmitted through bone
Overall --> MINIMIZES BENDING STRESSES on plate***
91
What is the point at which material begins to undergo plastic deformation?
yield point/yield strength***
92
How is bending strength of a screw determined?
Pullout strength?
Strength of plate?
Torsional strength of nail?
Bending strength of nail?
Bending: inner/minor diameter ^3***
Pullout --> outer/major diameter ^2 ***
Plate strength: thickness^3 ***
Torsional strength of nail: radius^4***
Bending for nail: radius^4 for solid nail***
Radius^3 for hollow nail****
93
Standard vs MIPO plating for medullary and periosteal blood flow?
Standard plating = greater compromise in BOTH periosteal AND medullary blood flow***
94
Ortho manifestations of rickets?
Brittle bones w/ physeal cupping/widening***
Bowing of long bones***
Flattening of skull
Ligamentous laxity
Rachtic rosary ribs/enlargment of costal cartilage
Kypohosis***
95
Vit D resist Rickets
Vit D deficient rickets
Vit d Dependent rickets
Vit D resitant/Familial hypophosphatemic****
MOST COMMON HERITABLE FORM
Caused by INABILITY OF RENAL TUBULES TO ABSORB PHOSPHATE****
Can be X linked Dom, AD, AR
X-linked dominant**** (most common form**) --> PHEX gene****
Increased levels of FGF23 --> decreases renal PO4 absorption and suppresses renal hydroxylase activity***
AD: mutation in FGF23***
AR: mutation in Dentin Matrix protein 1 (DMP1 gene)***
Vitamin D deficient/nutritional***
Decreased dietary intake of vit D (kids who are breastfed after 6 months, celiac)
Low Vit D --> decreased intestinal absorption of Ca --> Low Ca leads to high PTH and bone resporption --> HIGH ALP***
Vit D-dep't (Type I and II)
Type I: AR mutation in renal 25-OH-1alpha hydroxylase***
hypotonia, muscle weakness, fx early in life, hypocalcemia seizures
Type II: AR mutation in INTRACELLULAR receptor for 1,25 OH vit D***, similar sx as above (also get dental caries)
96
Female patient presents with signs/sx of Ricket. Got Vit D without improvement. Ca, PTH, vit D normal. Inheritance?
X-linked dominant*** (most common form)
X linked hypophophatemic rickets***
97
Type I vs Type II vitamin D dep't rickets?
Type I: deficiency of enzyme found in kidney***
Type II: inactivating mutation for rectory of 1,25 OH2 vitamin D3****
98
What is strongest indicator for compression fx in postmenopausal women?
History of 2 vertebral compression fractures***
99
Osteopenia T score? Osteoporosis?
Osteopenia T score -1 to -2.5*** (below peak bone mass of 25 y/o individual)
Osteoporosis T score
100
Who to treat with pharmacologic tx for osteopenia/osteoporosis?
Postmenopausal women and men >50 y/o with:
T score -1 to -2.5 at femoral neck/spine AND
-10 year risk of hip fx >/= 3%****
10 year risk of major osteoporosis fx >/= 20%****
T score < 2.5 at femoral neck/spine***
101
Calcium and vit D levels to take?
Age 9-18 y/o = 1000-1500 mg/d Ca***
>50 y/o = 1200-1500 mg/day***
Vit D: 800-1000 IUs vitamin D***
102
Non-nitrogen containing bisphosphanates
Mechanism?
Names?
Mech: Produces TOXIC ATP analogue***
Etidronate, clodronate, tiludronate (CTE)***
103
Nitrogen containing bisphosphanates
Mechanism?
Names?
Mech: Inhibit farnesyl pyrophosphate synthase (mevalonate pathway)*** --> INHIBITS GTPase**** (protein prenylation)
```
Pamidronate
Alendronate (Fosamax)
Risedronate (Actonel)
Zolendronate (Reclast)
Ibarndronate (Boniva)
```
104
What to treat vertebral compression fx with (pharmacologic)
Calcitonin*** (injection or nasal spray - destroyed by gastric acid)
105
What is Romosozumab? When used?
Romosozumab = Humanized monoclonal Ig2 --> activates Int pathway by BINDING SCLEROSTIN (sclerostin normally inhibits Wnt pathway) --> bone formation
use if failed or intolerant to other osteoporosis tx's
106
What % of BMD has to be lost to see on plain XR?
30-40% ***
107
With aging there is loss of what type of bone?
Trabecular bone loss more than cortical bone loss***
108
Drugs that increase risk of osteoporosis?
```
Phenytoin
oral steroids
Aromatase inhibitors***
Protease inhibitors***
SSRIs***
```
109
Type of crystal seen in gout?
XR?
Pseudogout crystals?
Monosodium urate crystal***
Negatively birefringent***
Needle shaped INTRACELLULAR crystals
Yellow when aligned parallel to red compensator, blue when aligned across direction of polarization***
XR: punched out periarticular erosion with sclerotic overhanging borders***
XR: also can see Soft tissue crystal deposition --> top***
Pseudogout crystals = weakly positively birefringent rhomboid shaped crystals***
110
Immunology of RA?
Cell mediated*** (T cell MHC type II***) immune response against soft tissue, then cartilage, then bone***
Rheumatoid factor = IgM ab against native IgG** --> immune complex then deposited in ed tissue like kidney as part of pathophys**
IgM targes Fc portion of IgG**
Mononucelar cells = primary cellular mediator of tissue destruction in RA
IL-1, TNF-alpha = part of cascade that leads to joint damage***
Ass'd with HLADR4**
111
What conditions have acetabular protrusio?
RA***
Marfans***
Paget's***
112
Most sensitive and specific test for RA?
Anti-CCP***
113
How does MTX work?
Folate analogue*** w/ anti inflammatory prop linked to inhibition of neovascularization
Therapeutic effects increased when combined w/ tetracyclines (Doxy***)--> due to anti collagenase properties***
114
How does Etanercept work?
Infliximab?
Adalimumab
Golimumab?
Etanercept: TNF-alpha receptor fusion protein --> binds to TNF-alpha***
Infliximab: Human/mouse chimeric anti TNA alpha MONOCLONAL Ab***
Adalimumab: Human anti TNF-alpha monoclonal Ab
Golimumab: Human anti TNF-alpha monoclonal Ab
115
How does anakinra work?
IL-1 receptor antagonist***
116
How does rituximab work?
CD20 monoclonal Ab*** --> inhibits B cells**
117
how does tocilizumab work?
Monoclonal Ab vs IL6 receptor***
118
How long to hold etanercept for surgical procedure?
Rituximab?
Adalimumab?
Infliximab?
Etanercept, adalimumab and infliximab approx 2 weeks***
Rituximab (CD20) --> 7 months**
119
Tx of RA foot?
1st MTP fusion + lesser metatarsal head resections***
120
What to think about with multi level cervical changes and sub axial subluxations at multiple levels?
RA patient***
121
Most significant risk factor for SSI in RA patient?
Previous SSI***
122
What is Vaughn-Jackson syndrome?
Rupture of hand digital extensor tendon string on ulnar side of wrist first and then moving radially (in RA patients) ***
123
What extensor tendon is at risk of rupture in RA patient at wrist?
Extensor digit quinti/minimi***
At high risk since it is overlying the ulnar head where it is prone to attritional rupture --> Vaughan-Jackson syndrome***
124
Most common cause of shoulder Charcot joint?
Syringomyelia***
125
How does heparin work?
Enhances ability of Antithrombin III to inhibit IIa, II, Xa***
126
How does lovenox work
Enhances ability of ATII to inhibit Xa*** (primary effect) and IIa (thrombin) (less effect)
127
How does fondaparinux work?
Indirect Xa inhibitor --> works though ATIII***
128
how do rivaroxaban, apixaban and edoxaban work?
Direct Xa inhibitors***
vs fondaparinux - indirect Xa inhibitor (through ATIII)
Half lives:
Rivaroxaban - 8 hours***
Apixaban - 12 hours***
129
How does Dabigatran work?
Direct thrombin inhibitor***
DaBigatran inhibits thromBin***
130
Reversal agent for heparin?
Protamine sulfate***
131
How does warfarin work?
Drugs that adversely affect?
Inhibits vitamin K 2,3 epoxide reductase***
Vit K needed for gamma carboxylation of glutamic acid for factors:
II (prothrombin), VII (first affected), IX, X
Also Protein C and protein S
```
Reaction w/ drugs:
Rifampin
Pheonbarbital
Diruetics
Cholestyramine
```
132
How does TXA work?
Antifibronlytic --> promotes clot formation
COMPETITIVELY inhibit activation of PLASMINOGEN by binding to the LYSINE binding site****
133
What is factor Ia? What can block its action?
Factor IA = fibrin***
Fibrin needs PLASMIN to degrade products, so TXA blocks activation of plasmin by competitively blocking plasminogen**
134
What is half life of warfarin?
36-42 hours***
135
Fat emboli syndrome - how to dx?
tx?
```
Major criteria:
Hypoxemia (PaO2 <60)***
CNS depression/changes in mental status***
Petechial rash***
Pulmonary edema
```
Tx:
Mechanical vent w/ high levels of PEEP***
Prevention
Early fx stabilization*** (fixation w/in 24 hours is strongest factor to prevent FES)
136
Types of CRPS?
How to prevent CRPS?
Type I: CRPS w/o demonstrable nerve, most common***
Type II: CRPS w/ evidence of identifiable nerve damage (causalgia)***
Vitamin C 500 mg x 50 days in DRF***
Also shown to decrease CRPS following F&A surgery***
137
What to think with osteopenia of patella?
CRPS of knee***
138
What are the three phases of bone scan?
Phase I (2 min) --> arteriogram
Phase II (5-10 min) --> cellulitis and synovial inflammation
Phase III (2-3 hours) --> bone images
CRPS: increased uptake in ALL phases, but phase III is most sensitive
139
How does Factor V Leiden work?
Normal factor V is cofactor to Factor Xa --> together they produce thrombin and drive coagulation
protein C regulates process --> inhibits factor V to prevent hyper coagulability***
Factor V Leidin can not be inhibited by protein C --> hypercoaguable***
140
What is hypophosphatasia?
Genetics?
Labs?
Metabolic bone dz characterized by generalized impairment of bone mineralization
Low levels of ALP --> decreased synthesis of inorganic phosphate necessary for bone matrix formation --> osteoid fails to mineralize***
Genetics: AR***
Mutation in TNSALP*** (tissue nonspecific isoenzyme of alkaline phosphatase)***
Labs: DECRASED ALP***
High urine phosphate output***
NOT always decreased serum phosphate (don't use as diagnostic)***
Urine: Phopspethanolamine*** (diagnostic for hypophosphatasia)**
141
How does indomethacin work?
Acts on lipoxygenase side of AA pathway --> inhibits leukotriene inflammatory mediators (vs other COX --> inhibit release of prostaglandins**)
142
half life of ASA?
1 week***
143
how do corticosteroids inhibit formation of effectors of inflammatory pathway?
Inhibit phospholipase A2***
Prevent the pre-inflammatory mediators AA by inhibiting phospholipase A2 --> earliest step in inflammatory cascade
144
Best way to achieve pain control in obese patent?
PCA --> based on patient's IDEAL WEIGHT***
145
How does acetaminophen work?
Not fully understood but does INHIBIT PG SYNTHESIS***
Inhibits PGE2 production through INTERLEUKIN-1 BETA*** (question on orthobullets)***
146
How do lidocaine and buipivicaine work?
Adverse effect with intra-articular infusion?
Interfere w/ nerve conduction to provide reversible loss of sensation --> affect depolarization phase of action potentials (cells fail to depolarize enough to fire after excitation leading to blocked action potential)***
Intra-articular infusion: Chondrolysis***
147
Prescription dosing for UE surgery
No narcotics
Trigger finger, nonop Dupuy's release**
10 narcotic tabs
Mucous cyst, carpal tunnel***, deQuervain's, Dupuy's surgical release, small joint fusion***
20 tabs
Wrist ganglion cyst, hand fx ORIF, LRTI, tendon transfers***
40 tabs
Large trauma, wrist fusion, open carpal surgery, DRUJ recon***
148
How does gabapentin work?
Binds Presynaptic Ca channels*** --> inhibits release of neurotransmitters***
149
Issue with using nitrous oxide during spine or pelvic procedures?
Increased gaseous abdominal distention --> more difficult imaging***
150
Intrascalene block
Used for shoulder/upper arm/elbow surgery***
Brachial plexus as it passes through groove between ANTERIOR and MIDDLE scalene muscles
complication: sensory neurapthy = most common***
151
Supraclavicular block
For arm and forearm (lower humerus down to hand)***
complications: pneumothorax***
152
Axillary block
Postop analgesia for surgery to elbow, forearm, wrist, hand**
153
Spinal vs Epidural vs combined spinal epidural?
All used for hip and knee arthroplasty
Spinal: single injection w/ 24 or 27 gauge needle
Complication: spinal headache (decreased with small needle), hematoma and opioid SE (N/V, pruritus, respiratory depression)
Epidural: indwelling Cath placed
complication: same as above
Combined: epidural needle placed into epidural space and spinal anesthesia through spinal needle followed by placing an epidural Cath
154
What to use to treat malignant hyperthermia?
Dantrolene*** (CCB)
155
Contraindications to bisphosphanates?
Severe renal dz --> excreted renal***
Following lumbar fusion***
156
What do nitrogen containing bisphosphonates bind to and inhibit?
Accumulate in high concentration in bones due to their binding affinity to HYDROXYAPATITE crystals***
Prevent protein prenylation through GTPase inhibition --> inhibits farnesyl diphosphate synthase***
157
Levels of evidence
Lvl I: RCT with >80% f/u
Lvl II: prospective cohort, poor f/u in RCT
Lvl III: retrospective cohort, case-control
Lvl IV: case series
Lvl V: expert opinion
158
What type of bias does intent to treat analysis help minimize?
Non-responder bias
159
How do cepahlosporins and PCN work?
BacteriCIDAL***
Competitive inhibition of transpeptidase enzyme***
160
How does Vanco work vs PCN?
PCN: compétitive inhibition of transpeptidase enzymes
Vanco: disrupts peptidoglycan cross linkage***
161
What are names of aminoglycosides? How do they work?
AG's: gent, tobra, streptomycin, neomycin
mech: Irreversibly bind to 30S SUBUNIT of ribosome***
162
Names of tetracyclines? Mech?
Doxycycline***, minocycline***
mech: Blocks tRNA in 30S ribosome***
163
Names of macrolides?
| Mech?
Azithromycin, erythromycin, clarithromycin***
Mech: Binds to 50S subunit***
Vs ahminoglycosides = 30S subunit (tobra, gent, streptomycin)***
164
How does clindamycin work?
Bacteriostatic***
inhibits 50S subunit (like macrolides like azithro,ertyro) and vs ahminoglycosides = 30S (tobra, gent)***
165
What class of abx inhibits fx healing?
Fluoroquinolones***
166
What does mech mutation do?
Bacterial gene encoding a PCN BINDING PROTEIN (PBP) --> less affinity to bind abx*** --> MRSA (resistance to methicillin etc)
167
What is D zone test?
for inducible CLINDAMYCIN resistance in staph and strep***
Do test on MRSA species prior to prescribing clinda**
168
How does linezolid work?
Binds to 23S portion of 50S ribosome --> prevents INITIATION COMPLEX between 30S and 50S subunits of ribosome****
169
What vaccines for splenectomy patient?
```
Pneumococcal
H flu
Menigococcal
Influenza
Lifelong ppx abs (erythro or PCN)***
```
170
How does amphotericin work?
Binding sterols and disrupts cell membrane***
171
Max amount of abx that can be added to cement?
5% overall***
So 40 g PMMA = 2 gram of abx before has deleterious effects on mechanical strength***
Commercially available will only do 1 g/40 g PMMA
172
When to restart chemo after osteosarcoma resection?
18-21 days***
Substantial improvement in overall survival (no improvement if started sooner than 16 days)**
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