Week 4 Flashcards
1
Q
whats the most common soft tissue tumor of adulthood?
A
lipoma
2
Q
what gene might be involved in the formation of a lipoma
A
HMGA2 gene rearrangement
3
Q
where do liposarcomas frequently occur?
A
deep soft tissue of proximal extremities and retroperitoneum
4
Q
what ancillary study might be helpful in diagnosing a liposarcoma
A
FISH positive for amplification of MDM2 on chromosome 12
5
Q
what is the most common neoplasm in women?
A
uterine leiomyomas
6
Q
where do leiomyomas commonly occur?
A
- uterus
- erector pili muscles
- muscularis of gut
7
Q
what would an IHC test on a leiomyoma and leiomyosarcoma show
A
positive for muscle-specific actin, desmin, caldesmon
8
Q
leiomyosarcoma and occurrence by gendeer
A
W>M
9
Q
where do leiomyosarcomas occur
A
uterus, deep soft tissues of extremities, and retroperitoneum
10
Q
Rhabdomyomas are rare, but where would you find them?
A
- most often in head and neck of men 25-40
* heart of children (hamartoma)
11
Q
what would an IHC study show for a rhabdomyoma or rhabdomyosarcoma?
A
positive for muscle specific actin, desmin, and myoglobin/myogenein/myoD1
12
Q
what is the most common sarcoma of childhood and adolescence?
A
rhabdomyosarcoma
*can be seen in adults too
13
Q
what is a genetic abnormalities seen in synovial sarcoma
A
t(X,18)
14
Q
what is the pathophysiology of damage in osteoarthritis
A
mechanical wear and tear of joint/cartilage (avascular) -> loss of cartilage and joint space -> bone on bone wear (eburnation)
15
Q
what are some risk factors for osteoarthritis
A
- female
- obese
- trauma
- advanced age
16
Q
Osteoarthritis typically does not have significant inflammation or systemic symptoms. what are some key characteristic of pain associated with osteoarthritis?
A
- worse with use, worse as day progresses
* alleviated with rest
17
Q
when does reactive arthritis occur
A
post-GI or GU infection, usually young adults, esp males
18
Q
whats the classic triad of reactive arthritis?
A
- conjunctivitis
- urethritis
- arthritis
19
Q
what are common bacteria involved in reactive arthritis?
A
- shigella
- yersinia
- chlamydia
- campylobacter
- salmonella
20
Q
what protein is associated with reactive arthritis?
A
HLA-B27
21
Q
what is reactive arthritis?
A
- a seronegative spondyloarthropathy
* an autoimmune condition caused by cross-reactivity with bacterial antigens
22
Q
What protein is associated with rheumatoid arthritis
A
HLA-D4
23
Q
classic features of pain with rheumatoid arthritis
A
- symmetric
* improves with use; morning stiffness
24
Q
what is rheumatoid arthritis
A
autoimmune disease characterized by mainly chronic inflammatory cells in the synnovium and deposition of antigen complexes
25
what is the mechanism of joint destruction in rheumatoid arthritis
release of cytokines and inflammatory factors (including IL-1, IL-6, TNF-α) -> tissue damage and eventually erosion of adjacent bone and cartilage
26
what is a key joint that is spared in rheumatoid arthritis?
DIP
27
unlike osteoarthritis, Rheumatoid arthritis does have systemic signs and symptoms. What are they?
* rheumatoid nodules
* interstitial lung disease
* pericarditis
* anemia
* amyloidosis
* vasculitis
28
what testing can be used to diagnoses rheumatoid arthritis?
* rheumatoid factor (RF)
| * Anti-cyclic citrullinated peptide (anti-CCP) antibody (more specific than RF)
29
what is the cause of gout
hyperuricemia (underexcretion or overproduction) -> precipitation of monosodium urate crystals in joint
30
Who/what does gout typically affect?
* usually older men
| * typically one joint, especially MTP join
31
risk factors for gout
* obesity
* HTN
* diet (red meat, EtOH)
* DM
32
in polarized light, what will the crystals look like for gout
* yellow under parallel light
| * blue under perpendicular light
33
what kind of crystals are deposited in gout
* monosodium urate crystals
| * needle shaped
34
what kind of crystals are deposited in pseudo gout?
* calcium pyrophosphate
| * rhomboid shaped
35
demographic of pseudo gout
older patients, males and females
36
cause of pseudo gout
mostly idiopathic
37
most common joint to be affected by pseudogout
knee
38
what is osteogenesis imperfecta
disorder characterized by brittle bones, usually due to absent or low collagen Type I, or abnormal collagen
39
what mutations account for most cases of osteogenesis imperfecta
COL1A1 and COL1A2 genes
| others include SERFINF1 and PPIB
40
what are some signs of osteogenesis imperfecta
* blue sclera
* dentinogenesis imperfects
* hearing loss (abnormal/fractured ossicles)
41
inheritance of osteogenesis imperfecta
autosomal dominant, most are de novo
42
what is a sign of vertebral compression in osteoporosis
kyphosis
43
what is a common diagnostic test for osteoporosis
* DEXA (dual energy xray absorptiometry) scan
| * clinical - hx fx of hip or vertebrae +/- radiologic findings
44
what happens in osteoporosis
loss of trabecular and coritcal bone mass
45
What is primary osteoporosis
* age related
* type I - post menopausal women -> loss of estrogen
* type II - old age (men and women)
46
what is secondary osteoporosis?
due to drugs (ie steroids), hyperparathyroidism, or hyperthyroidism
47
pathophysiology of osteoporosis
•increased osteoclastic activity relative to osteoblastic activity
48
what happens in post-menopausal women who get osteoporosis
decreased estogen -> decreased osteoprotegerin (OPG) -> increased RANKL/RANK -> upregulated osteoclast activity
49
what is osteomalacia
defective mineralization of osteoid due to low vitamin D levels
50
risk factors for osteomalacia
* kidney and liver failure
* diet/malabsorption
* dark-skinned populations
* northern latitudes/low sunlight
51
pathophysiology of paget's disease
* abnormal osteoclast activity -> abnormally formed and weak bones
* osteoblasts activity and overcompensation -> disorganized bone formation -> osteosclerosis
52
long term paget's disease can lead to
* arteriovenous shunts in bone
| * high output cardiac failure
53
patients with paget's disease are at increased risk for
osteosarcoma
54
what are lab values that will be seen with pagets disease
* alkaline phosphatase ELEVATED
* PTH normal
* calcium normal
* PO4 normal
55
histologic features seen in paget's disease
irregular mosaic pattern of bone formation
56
patients with paget's disease may complain of (esp men)
increased hat size
57
rickets can be seen in children. what is it?
defective mineralization of osteoid due to low vitamin D and defective mineralization of cartilage in growth plate - weak/soft bones
58
what are some clinical findings in rickets
* epiphyseal widening
* bowing of bones (genu varum)
* rachitic (ribcage) rosary
* fxs
* soft skull (craniotabes)
* frontal bossing
* pigeon breast defromity
* muscle spasms
59
what are some risk factors for rickets?
* diet/malabsorption
* dark-skin
* northern latitudes/ low sunlight
* breast feeding w/o vit d supplementation
60
what is osteomyelitis
infection of bone and bone marrow; majority are bacterial
61
risk factors for osteomyelitis
DM, vascular disease, IV drug use
62
how does infection spread to bone in osteomyelitis for children
•hematogenous spread, associated with bacteremia
63
what bones are most affected in osteomyelitis for children
long bone, especially metaphysis
64
how does infection spread to bone in osteomyelitis for adults
* often caused by injury exposing bone to infectious organism
* or spread of nearby soft tissue infection (contiguous)
65
bones most affected by osteomyelitis in adults
* vertebrae (esp in tuberculosis)
* pelvis
* feet
66
what is the most common organism responsible for osteomyelitis?
staph. aureus (80-90%)
67
what organism might be implicated in osteomyelitis for patients affected by sickle cell disease?
salmonella
68
what organism might be implicated in osteomyelitis for patients who are young and sexually active?
N. gonnorhea
69
what organisms might be implicated in osteomyelitis for patients affected by diabetes, IV drug use, GU infections?
pseudomonas and E. coli
70
what organism might be implicated in osteomyelitis for patients who have had animal bites/scratches?
pasturella
71
what organism might be implicated in osteomyelitis for neonates?
H. influenza or group b streptococcus
72
what are some radiologic findings you might see in osteomyelitis?
* cloaca
* sequestrum
* involucrum
73
what is a cloaca
* possible radiologic finding in osteomyelitis
| * cortical defect formed due to increased pressure in bone from abscess formation/suppurative inflammation
74
what is a sequestrum
* possible radiologic finding in osteomyelitis
| * fragment of dead infected bone, which is resistant to treatment by abx and immune cells
75
what is a involucrum
* possible radiologic finding in osteomyelitis
| * reactive bone and inflammatory cells and reactive tissue surrounding sequestrum
76
what mutation is found in achondroplasia
FGFR3 mutation
77
what happens with the FGFR3 mutation in achondroplasia
it is an activation mutation that leads to premature closure of growth plate
78
what bones are affected in achondroplasia
long bones, which undergo endochondral ossification
79
what bones are spared in achondroplasia
bones which undergo membranous ossification (eg skull and pelvis)
80
most common inheritance of achondroplasia
* Autosomal dominant
| * most are inherited from unaffected father as de novo mutation
81
what are histologic findings associated with osteopetrosis
* lack of bone marrow elements (hematopoietic cells)
| * replacement of bone marrow by dense, irregular bone
82
mutations associated with osteopetrosis lead to functional abnormalities in what cell type
osteoclast (lack of function)
83
what is osteopetrosis
defect in bone resorption leading to thick, dense, yet fragile bone
84
what are some mutations associated with osteopetrosis
* carbonic anhydrase II
* CLCN7
* TCIRG1
85
what is the CLCN7 gene important for
* part of HCl ion exchange channel
| * mutated in most cases of pure osteopetrosis
86
what gene is second most commonly mutated in osteopetrosis
TCIRG1
87
a mutation in carbonic anhydrase II is part of a syndrome of
osteopetrosis and renal tubular acidosis
88
signs and symptoms of osteopetrosis include
* broken bones
* anemia, thrombocytopenia, leukopenia (replacement of bone marrow)
* vision and hearing problems
* facial paralysis
* short stature
89
what is the treatment for osteopetrosis
bone marrow transplant
90
examples of benign tumors of the epiphysis
* chondroblastoma
| * giant cell tumor
91
examples of benign tumors of diaphysis
* endochondroma
| * fibrous dysplasia
92
examples of malignant tumors of diaphysis
* ewing sarcoma
| * chondrosarcoma
93
examples of malignant tumors of metaphysis
* osteosarcoma
| * juxtacortical osteosarcoma
94
examples of benign tumors of metaphysis
* osteoblastoma
* osteochondroma
* non-ossifying fibroma
* osteoid osteoma
* chondromyxoid fibroma
* giant cell tumor
95
most common cancer types to metastasize in bone
```
BLT with a Kosher Pickle
•breast
•lung
•thyroid
•kidney
•prostate
```
96
what kind of bone tumors are usually seen in metastatic disease
* usually osteolytic
| * but can be osteoclastic (sclerotic), esp prostate
97
enchondroma (or chondroma) is a type of primary bone tumor of cartilage (intraosseous cartilage). What mutations are associated?
IDH1 and IDH2
98
osteochondroma is a primary bone tumor (cartilage-capped tumor with bony stalk). What mutations are associated?
EXT1 and EXT2
99
Chondrosarcoma is a primary bone tumor of cartilage. What mutations are associated?
IDH1 and IDH2
100
what is fibrous dysplasia
a benign tumor with normal bone components that don't mature (key word* look like chinese characters)
101
what mutation might be associated with fibrous dysplasia
GNAS mutation, monostotic vs polyostotic
102
McCune Albright syndrome can be associated with cafe au lait spots, precocious puberty in girls, hyperthyroidism and acromegaly. What bone abnormality can occur?
fibrous dysplasia, monostotic or polyostotic
103
What bone benign tumor can be found with gardner syndrome?
osteoma
| Gardner syndrome = FAP with osteomas and epidermal cysts
104
Aside from osteomas and fibrous dysplasia, what are some other benign tumors that produce bone/osteoid
* osteoid osteoma
| * osteoblastoma
105
ewing sarcoma is classified as a primary bone tumor without matrix formation (bone or cartilage). What mutation is associated?
t(11,22)
106
Giant cell tumor of bone is classified as a primary bone tumor that does not form matrix (bone or cartilage). What mutation is associated?
H3F3A
107
what would be seen on a radiologic image of chondrosarcoma
stippled or popcorn-like calcification and endosteal scalloping
108
common sites for chondrosarcoma
* pelvis/shoulder/ribs
* femur
* humerus
109
where in a bone would you expect to find chondrosarcoma
begins in metaphysis and extends to diaphysis
110
what symptoms would be seen with chondrosarcoma
constant pain that is not relieved with rest
111
what would be seen histologically in chondrosarcoma
* disordered arrangement of chondrocytes within clear lacunae, surrounded by a bluish matrix
* increased cellularity and atypia
112
what's the demographic most affected by osteoid osteoma, which is a benign bone forming tumor?
males in teens and 20s
113
bones most commonly affected by osteoid osteoma
femur or tibia; tumor is <2 cm
114
presentation of osteoid osteoma
pain, esp at night, relieved with aspirin/NSAIDS
115
what is the cause of pain in osteoid osteoma?
prostaglandins produced by the tumor, which is why aspirin helps the pain
116
what would be seen on a radiologic image of osteoid osteoma
small radiolucent nidus surrounded by sclerotic bone
| nidus is the tumor, sclerotic bone is reactive
117
what is seen histologically in osteoid osteoma
interlacing trabeculae of woven bone lined by osteoblasts
118
how can osteoblastoma be differentiated from osteoid osteoma?
```
in osteoblastoma
•tumor is >2cm
•often in posterior spine
•does not have sclerotic border
•pain not relieved by aspirin
```
119
Giant cell tumors are benign, but locally aggressive. What is the demographic typically affected
F>M, 20s to 40s
120
typical locations of giant cell tumors
usually in epiphyses of long bones (distal femur, proximal tibia, and distal radius)
121
giant cell tumors can become malignant in 2-3% of cases. Where might metastases occur
in 1-9% of cases, distant mets occur. most often in lungs - "benign pulmonary implants"
122
what is the presentation of giant cell tumors
usually pain and swelling
123
what would be seen in radiologic image of giant cell tumor
expanding lytic lesion without sclerotic rim
124
what would be seen histologically in giant cell tumor
multinucleated cells (not neoplastic) in background of uniform mononuclear cells (neoplastic primitive mesenchymal cells)
125
t(11,22) is present in ewing sarcoma. What important gene movement occurs
EWS gene moved from chromosome 22 to the FLI1 gene on chromosome 11
126
Ewing sarcoma is a malignant tumor with primitive round cells (no differentiation) what demographic does it affect
children
127
where does ewing sarcoma occur
usually diaphysis of long bones
128
presentation of ewing sarcoma
painful, enlarging mass; may be warm and tender (mimic infection)
129
what would be seen on a radiologic image of ewing sarcoma
destructive lytic tumor with moth-eaten margins, extending into soft tissues
130
what would be seen histologically in ewing sarcoma
sheets of primitive, small round blue cells
131
What ancillary studies could be used in diagnosis of ewing sarcoma
* IHC positive for CD99
| * FISH positive for EWSR1 gene rearrangement, usually t(11,22), EWSR1 and FLI1
132
osteosarcoma is a malignant bone tumor that produces bone matrix. What is the primary demographic affecgted
* <20 year olds
* M>F
* second peak in older adults, with predisposing conditions (paget disease, bone infarcts, prior radiation)
133
presentation of osteosarcoma
* painful, enlarging masses
| * may present with pathologic fracture
134
location of osteosarcoma
usually in metaphysis of long bones (esp around knee)
135
radiologic findings in osteosarcoma
* large infiltrative destructive mass
| * mass often breaks through cortex and lifts periosteum (codman triangle) or extends into soft tissue
136
histologic findins in osteosarcoma
pleomorphic cells with hyperchromatic nuclei which make bone
137
how does aspiring work?
irreversibly inhibits prostaglandin biosynthesis by acetylating cyclooxygenase (COX)
138
What are DMARDs
* Disease-modifying antirheumatic drugs
| * mitigate (and possibly reverse) damage due to reduction in inflammatory mediators
139
Biologics are a type of DMARD. what types are there
* cytokine blokers
* inhibitors of T cell activation
* inhibitors of B cell function
140
how does methotrexate work in cancer
competitively inhibits dihydrofolate reductase (DHFR) an enzyme that participates in tetrahydrofolate synthesis (folic acid needed for purine synth)
141
what does methotrexate do in treatment of RA (and other autoimmune diseases)?
* inhibits enzymes involved in purine metabolism
* inhibition of T cell activation and suppression of intracellular adhesion molecule expression by T cells
* selective down regulation of B cells
142
Leflunomide can be used in treatment of RA. what does it do
•inhibition of dihydroorotate hydrogenase, which inhibits uridine monophosphate synthesis and ultimately pyrimidine synthesis
143
side effects of leflunomide
* liver damage (esp if on methotrexate too)
* lung disease
* birth defects
144
Infliximab can be used in RA treatment. what does it do
cytokine blocker; it is a chimeric anti-TNF-α monoclonal antibody
145
Etanercept can be used in RA treatment. what does it do
cytokine blocker (specifically anti-TNF agent); human TNF receptor linked to the Fc portion of a human IgG1
146
infliximab administration has been associated with an increased risk for
developing tuberculosis
147
anti-TNF therapy may have increased incidence of
* infection
* lupus
* exacerbation of demyelinating diseases (eg MS)
* heart failure
* increased incidence of lymphoma (may/may not be assoc)
148
what is the goal in therapy for osteoporosis
downregulating osteoclast activity
149
bisphosphonates can be used in treatment of osteoporosis, pagets disease, primary hyperparathyroidism, osteogenesis imperfecta, and metastatic carcinoma. How does it work?
* localized in calcium (bone), taken up by osteoclast
* then inhibits enzymes that induce apoptosis
* and alter pathways for intracellular protein trafficking, aspects of cytoskeleton, and maintenance of cell contact with bone
150
side effects of bisphosphonates
GI upset, esophagitis, osteonecrosis of jaw, atypical femoral fractures
151
how does denosumab work
* monoclonal antibody targeting RANKL on osteoblast
| * reduces RANKL-RANK interaction -> reduces osteoclastogenesis
152
what might cause decreased uric acid secretion
* idiopathic
* renal failure
* diuretics
153
what might cause increase uric acid in blood
* diet
* tumor lysis
* trauma
* lesch-Nyhan
154
what is the treatment of an acute flare of gout
symptomatic relief and reduction of inflammation
| -> NSAIDs, steroids, colchicine
155
Long term management of gout has the goal of
reduction of uric acid levels
156
how does colchicine work
* inhibits microtubule polymerization and neutrophil chemotaxis
* degranulation
157
role of aspirin in gout
* High dose aspirin can help treatment -> inhibits tubular reabsorption of uric acid
* low dose aspirin can cause flare
158
what does allopurinol inhibit
xanthine oxidase, which catalyzes hypoxanthine -> xanthine -> plasma uric acid
159
how does probenecib work?
inhibits tubular reabsorption of uric acid
160
what are type 1 muscle fibers
| one slow red ox
* slow contraction; capable of endurance
* high in oxidative activity; low in glycolytic activity
* red bc high myoglobin and high mitochondrial content
161
what are type 2 muscle fibers
| two fast white sugar
* fast contraction; fatigue quickly
* low oxidative activity; high in glycolytic activity
* white grossly
162
histopathological features of neurogenic atrophy
* fiber type grouping
| * group atrophy
163
histopathological features of disuse/steroid atrophy
type II myofiber atrophy
164
histopathological features of dystrophin related myopathy
* myofiber size variability
* necrosis
* regeneration
* endomysial fibrosis
* fatty replacement
165
histopathological features of inflammatory myopathy
* inflammation (usually T cells)
* necrosis
* regeneration
166
histopathological features of congenital myopathy
* wide variety of specific changes, inclusions, etc
* nemaline rods
* central cores
167
histopathological features of channelopathies
may be normal
168
clinical clues for neurogenic atrophy
nerve damage (often associated with sensory features)
169
clinical clues for disuse/steroid atrophy
* bedridden/icu
* corticosteroids
* hyperthyroidism
170
clinical clues for dystophin related myopathy
childhood onset
171
clinical clues for inflammatory myopathy
* adult onset
| * associated rheumatologic features
172
clinical clues for congenital myopathy
onset at birth; floppy infant
173
clinical clues for channelopathies
* myotonia
| * intermittent symptoms
174
etiology of neurogenic atrophy
moto nerve damage
175
etiology of disuse/ steroid atrophy
atrophy of fast twitch (type 2) fibers
176
etiology of dystrophin related myopathy
hereditary abnormalities of dystrophin related proteins
177
etiology of inflammatory myopathies
autoimmune
178
etiology of congenital myopathy
variable
179
etiology of channelopathies
muscle sodium channel protein SCN4A defect
180
myopathic pattern often associated with
scattered myofiber necrosis and regeneration
181
inflammatory myopathy patterns are myopathic, but also characterized by
inflammatory infiltrates and/or intracellular inclusions
182
cushing syndrome cause endogenous exposure to
glucocorticoid -> steroid atrophy
183
hyperthyroidism can cause what type of atrophy
type II myofiber atrophy (like disuse and glucocorticoid)
184
what is the dystophin-glycoprotein complex
skeletal muscle membrane associated proteins involved in the mechanical stabilization and signaling interactions between cytoskeleton, membrane, and ECM
185
what is gower's sign and what is it a key clinical sign of
* sign of duchenne muscular dystrophy
| * pt uses hands to "walk" up their own body to stand from a sitting position due to muscle weakness in thigh and hip
186
congenital myopathies often result in relatively static deficits. Examples of these deficits include
* central core disease
* nemaline myopathy
* centronuclear myopathy
187
ion channel myopathies are familial disorders that are characterized by
* myotonia
| * relapsing episodes of hypotonic paralysis associated with abnormal serum potassium levels
188
hyperkalemic periodic paralysis is an inherited disorder involving mutations in
skeletal muscle sodium channel protein (SCN4A, chromosome 7) -> regulates sodium entry during contraction
189
malignant hyperthermia is a rare syndrome, but can result in death from
anesthetic agents or succinylcholine during surgery
190
mitochondrial myopathies can stem from mitochondrial or nuclear inheritance. usually manifest
* early adulthood
| * proximal muscle weakness and sometimes severe involvement of ocular musculature
191
what is polymositis
* inflammatory myopathy
* associated with T-cell and increased expression of MCH 1 on myofibers
* successful treatment with corticosteroids
192
dematomyositis is most common inflammatory myopathy in
children
193
dematomyositis is believed to have an autoimmune basis.f what happens
myofiber damage in a paraseptal or perifascicular pattern
194
inclusion body myositis is most common inflammatory myopathy in
patients older than 60
195
morphologic hallmark of inclusion body myositis
rimmed vacuoles that contain aggregates of same proteins that accumulate in brains of pts with neurodegenerative disorders
196
key in treatment of inclusion body myositis
does not respond well to immunosuppressive agents
197
thyrotoxic myopathy
* acute or chronic proximal muscle weakness
| * myofiber necrosis and regeneration
198
ethanol myopathy
* after binge drinking
* complain of acute muscle pain
* myocyte swelling, necrosis, and regeneration
199
drug myopathy
* statins common
| * affected muscles usually show evidence of myopathic injury, usually without inflammatory component
