September 9 Bone Path Flashcards
What is the most common soft tissue tumor in adults?
Lipoma
What is the most common soft tissue tumor in adults?
Lipoma
What is the most common sarcoma in adults?
Liposarcoma
What is Rhabdomyosarcoma common in?
Kids
Lipoma
12q14-12q15 aberations -most common soft tissue tumor adults -solitary (unless rare hereditary) -painless and unmoving (unless angiolipoma) -soft yellow encapsulated masses -histo looks normal
Liposarcoma
-most common sarcoma in adults -deep soft tissues proximal extremities/retroperitoneum -histo=lipoblasts (scalloped vacuoles) WELL DIFFERENTIATED: supernumery ring chromosomes (12q14-q15 w/ MDM2 amplification) MYOXOID/ROUND LPS: t(12;16)(q 13;p11) = FUS CHOP gene PLEOMORPHIC: most agressive
Lipoblastoma
Kids Lipoblasts PLAG1
Hibernoma
Kids, brown fat tumor
Fibromatoses
SUPERFICIAL: palmar (Dupuytren contracture), plantar=on tendon sheaths -penile (Peyronie disease)=curvature penis Stabilize, could resolve DEEP SEATED/DESMOID: between benign fibrous tumors and fibrosarcoma Reoccur Teens-30s Gardner sx APC/B catenin mutations
Fibrosarcoma
Malignant, fibroblasts Adults Deep in thigh, knee, retroperitoneum Agressive Vimentin=marker?
What is the most common neoplasm in women?
Uterine leiomyomas
Leiomyosarcoma
10-20% soft tissue sarcomas F>M sin, deep soft tissues extremities/retroperitoneum Usually good if superficial
Rhabdomyosarcoma
Most common soft tissue disease in kids Head, neck, genitourinary TYPES: Embryonal, alveolar, pleomorphic
Embryonal Rhabdomyosarcoma
49% rhabdomyosarcoma
Head, neck (orbital and parameningeal), GU track
DEEP extremities, pelvis, retroperitoneum
Loss of 11p15, extra 8, 12, 13 and/or 20
Botryoids in female girl vaginas
Alveolar Rhabdomyosarcoma
31% rhabdomyosarcoma; 10-25 yo Deep soft tissues and EXTREMITIES!!!! PAX gene translocation -t(2;13)/PAX3-FKHR -t(1;13)/PAX 7-FKHR Alveolar growth pattern
Synovial Sarcoma
5-10% of soft tissue tumors Young adults, males 80% in deep soft tissue extremities around KNEE t(x;18)(p11;q11) w/ SYT SSX1 or SSX2 On MRI see calcifications, mass behind knee Treat with limb sparing surgery, chemo Metastasis lung, bone, lymph nodes 20% live >10 years
Pseudosarcomatous Proliferation
Idiopathic/trauma induced non neoplastic lesions that mimic sarcoma Nodular fascitis –> tumor after trauma on extremities; clonal chromosomal changes/big nuclei Myositis ossificans –> proximal extremities in young adults; trauma >50% cases *metaplastic bone that ostifies and gets filled w/ marrow
What is the most common sarcoma in adults?
Liposarcoma
What is Rhabdomyosarcoma common in?
Kids
Lipoma
12q14-12q15 aberations -most common soft tissue tumor adults -solitary (unless rare hereditary) -painless and unmoving (unless angiolipoma) -soft yellow encapsulated masses -histo looks normal
Liposarcoma
-most common sarcoma in adults -deep soft tissues proximal extremities/retroperitoneum -histo=lipoblasts (scalloped vacuoles) WELL DIFFERENTIATED: supernumery ring chromosomes (12q14-q15 w/ MDM2 amplification) MYOXOID/ROUND LPS: t(12;16)(q 13;p11) = FUS CHOP gene PLEOMORPHIC: most agressive
Lipoblastoma
Kids Lipoblasts PLAG1
Hibernoma
Kids, brown fat tumor
Fibromatoses
SUPERFICIAL: palmar (Dupuytren contracture), plantar=on tendon sheaths -penile (Peyronie disease)=curvature penis Stabilize, could resolve DEEP SEATED/DESMOID: between benign fibrous tumors and fibrosarcoma Reoccur Teens-30s Gardner sx APC/B catenin mutations
Fibrosarcoma
Malignant, fibroblasts Adults Deep in thigh, knee, retroperitoneum Agressive Vimentin=marker?
Smooth muscle tumor characteristics
What is the most common neoplasm in women?
Uterine leiomyomas
Leiomyosarcoma
10-20% soft tissue sarcomas F>M sin, deep soft tissues extremities/retroperitoneum Usually good if superficial
Rhabdomyosarcoma
Most common soft tissue disease in kids Head, neck, genitourinary TYPES: Embryonal, alveolar, pleomorphic
Embryonal Rhabdomyosarcoma
49% rhabdomyosarcoma;
Alveolar Rhabdomyosarcoma
31% rhabdomyosarcoma; 10-25 yo Deep soft tissues and EXTREMITIES!!!! PAX gene translocation -t(2;13)/PAX3-FKHR -t(1;13)/PAX 7-FKHR Alveolar growth pattern
Synovial Sarcoma
5-10% of soft tissue tumors Young adults, males 80% in deep soft tissue extremities around KNEE t(x;18)(p11;q11) w/ SYT SSX1 or SSX2 On MRI see calcifications, mass behind knee Treat with limb sparing surgery, chemo Metastasis lung, bone, lymph nodes 20% live >10 years
Pseudosarcomatous Proliferation
Idiopathic/trauma induced non neoplastic lesions that mimic sarcoma Nodular fascitis –> tumor after trauma on extremities; clonal chromosomal changes/big nuclei Myositis ossificans –> proximal extremities in young adults; trauma >50% cases *metaplastic bone that ostifies and gets filled w/ marrow
Four categories of osteomyelitis?
Hematogenous: bacteria in bone bc previous infection (kids) Direct implantation: penetrating injury Continguous: spread of bacteria from ulcer/wound (adults) Inf of prosthetic device: bacteria in bone from inf of prosthetics (adults)
Hematogenous Osteomyelitis
Bone becomes “loose”; can occur in spine Staph aureus, strep sp., gram -, mycobacterium tuberculosis, salmonella in sickle cell pts
Direct implantation Osteomyelitis
Occurs from pseudomonas and other organisms
Contiguous osteomyelitis
S. Aureus, gram -, strep sp., anaerobes, Candida Bacteria in bone different than in ulcer!
Prosthetic Joint Infection Osteomyelitis
Coagulase - staph, S. aureus, gram -, strep sp. (hard to treat!)
General characteristics of osteomyelitis
Chronic infections lead to no fever Sequestrum=dead bone Involucrum=new bone Brodie’s abscesses=abcesses in bone due to bacteria
Biofilms
Aggregations of microorganisms to surface of something Embedded in matrix of “slime”, glycocalyx (tubes) More resistant to antibiotics/different properties than normal bacteria Coagulase - good at!
Treatment for Osteomyelitis
Rifampin= RNA inhibitor (good for biofilms and S. aureus) Antibiotics only helpful if tissue still there (oral for joint infections)
What is this?
Gout
Urates on the articular surface, destroy cartilage
Fuzzy crystals under microscope
What is the inflmmatory response of gout
The inflammasome eats/detects the MSU
IL1B is activated
Inflammatory cascade with neutrophils occurs
What are the categories of treatment for gout?
NSAIDS (NO ASPIRIN; indomethacin, naproxen)
Corticosteroids (short term if can’t take NSAIDS)
Colchicine, allopurinal, febuxostat, pegloticase, probenecid
Colchicine
Used for gout
No effect on uric acid excretion but antimiotic
–bind to tublin in neutrophils and inhibit; less pain
–oral, rapid absorption/good distribution
–activated by CYP450 and eliminated via P glycoprotein
–GI side effects
–Contraindictations –> elderly, hepatic/renal disease, CYP3A4/PgP inhibitors
What are some non-pharm ways of prophylaxis for treatment of gout?
Abstain from alcohol
Wt loss
No aspirin/thiazide
Allopurinol
Prevent gout flare up
Inhibit last steps in uric acid biosynthesis via blocking xanthine oxidase
Metabolized by aldehyde oxidoreductase oxypurinol (longer 1/2 life)
Can cause hypersensitivity OR gout by mobilizing uric acid
Febuxostat
Prevent gout flare up
Non-purine xanthine oxidase inhibitor
Vs allopurinol, it’s more potent, effective if you have impaired renal function BUT more adverse/CV effects
Pegloticase
Used for gout
Sends PEGylated uricase to humans
Makes uric acid to allantoin (H2O soluble)
Need to be given by IV
Can cause gout flare or immune response against PEG
Probenecid
Used for gout
Uricosuric agent; increases rate of excretion of uric acid
Compete with OAT so less uric acid reabsorbed
GI effets, bad if kidney issues/stones
Bad for use with drugs that need transporter (penicillin)
What is this?
Rheumatoid arthritis
Microscopic picture of papillary synovitis (pannus) with lymphoid infiltrates at the center
What is this?
Rheumatoid arthritis
Synovium hyperplasia with lymphocytes
What is this?
Rheumatoid nodule showing the central geographic
fibrinoid necrosis and the surrounding palisaded chronic
inflammatory cells
What are the general properties of DMARDs against rheumatoid arthritis?
Parental inj
Extracellular, does not cross BBB
Long half life, infreq. administration
Safe but immunogenicity against; increase risk for inf
Etanercept
Used for RA, all stages
Block TNFalpha by inhibiting ability to bind to receptor (only soluble)
Recombo fusion protein
Adalimumab
All stages RA
IgG human monoclonal Ab; binds to all forms TNFalpha to prevent binding
Tocilizumab
Anti RA; not first line
humanized ab that binds to soluble/membrane form IL6
Alterations lipid profile
Tofacitinib
Moderate-severe RA
Inhibitor of JAK (transcription factor that transcribes pro inflammatory genes)
Alters lipid profile
Oral
Rituximab
Mod/severe RA
Depletes B cells by binding to CD20 (eitehr CDC or ADCC)
Abatacept
Mod-severe RA
Inhibit binding to CD28 and activation of T cells by APC
contains CTLA4
fusion protein
Anakinra
RA mod/severe
Recombo protein that is a competitive antagonist of IL 1
What is this?
Early OA
Superficial layers of cartilage crack
Limited new matrix formed
What is this?
Subchondral cyst (geode) from late OA
What are the main treatment options for OA?
Main=wt loss, exercise, physical therapy (first line)
Corticosteroids/hyaluronans=injected; high placebo–last line before therapy
Topical: capsaicin, salicylates, menthol
Systemic: acetaminophen, duloxetine, NSAIDS
Opiods=NOT GOOD
Duloxetine
Used for OA
Oral, centrally acting
Causes inhibition of 5-HT/NE reuptake
See analgesic effect earlier than antidepression, and minor side effects only
Capsaicin
Used for OA
Topical, releases substance P, pain inhibiting effect; adverse=pain/erythema/site reactions/depletes sub P eventually
Glucosamine/Chondroitin
Dietary supplement for OA
Glucosamine=maintain cartilage integrity
Chondroitin=maintain joint viscosity and stimulate repair
Hyaluronic acid
Used for OA
Injection, endogenous, inhibit degregation of cartilage apparently but no good data
