PULM Week 4 Lectures Flashcards
(177 cards)
1
Q
list the origin of some air pollutants that affect the respiratory tract
A
- natural (sand)
- combution (vehicle exhaust, cig smoke)
- synthetic (consumer products such as phthalates–soft plastics)
- agriculture (grain dust)
- chemical reactions (anticipated and unanticipated)
- unknown (suspected in sarcoidosis)
- indoor (cleaning products)
- outdoor (ozone)
2
Q
describe patterns of exposure to airborne pollutants
A
- magnitude (large or small, insidious or accidental)
- context (occupational versus environmental)
- persistence (acute versus chronic)
- duration (steady versus intermittent, seasonal i.e ozone in the summer, diurnal i.e traffic related)
- geography (small versus large scale, valleys versus flats)
- conditions (exertion, personal protection)
3
Q
what determines the site of deposition of materials inhaled into the respiratory tract?
A
for gasses: dependent on water solubility
for solids: dependent on particle size or aerodynamic diameter
4
Q
what is a highly soluble gas? where its it major site of deposit?
A
NO2 (highly)
Ozone (slightly less so)
enters small airways, alveoli
5
Q
what is a less soluble gas? where does it deposit?
A
phosgene, SO2
deposits in upper airways/large airways, or lung parenchyma
6
Q
what is a very insoluble gas? where does it deposit?
A
ammonia
deposits in the nasopharynx
7
Q
where do solid large particles deposit
A
they are efficiently filtered by the nose
> 10 um
8
Q
where do medium solid particles deposit
A
in the trachea and large airways
3-10 um
9
Q
where do small particles deposit
A
in the alveolar space
0.1-3 um
10
Q
where do very small particles deposit
A
do not settle out from air stream and therefore poorly deposited at any location in the respiratory tract; many are exhaled
11
Q
how does aerodynamic diameter affect where solid particles deposit in the respiratory tract?
A
thin fibers will penetrate deeper
aerodynamic diameter is more important than length of fiber
explains why long asbestos fibers may penetrate deeply into the lungs
12
Q
list the ways in which airborne pollutants may damage the respiratory tract
A
- non-specific chemical reactivity
- specific cellular toxic effects
- mutations
- inflammation–>necrosis–>fibrosis
- allergic reactions (sensitization)
- oxidative stress mediates many of these effects, including cardiac effects
- interacting exposures can magnify effects
- clinical LATENCY is common
- remember–no part of RT is immune to exposures
13
Q
how does non specific chemical reactivity of airborne pollutants affect the respiratory tract
A
generate reactive oxygen species (NOx)–>oxidative stress
stong acids/bases (i.e sulfuric acid)
14
Q
describe the nature of some specific cellular toxic effects of airborne pollutants on the respiratory tract
A
- displace O2 by concentration gradient (i.e with CO2, methane, N2)
- interferes with O2 carrying capacity of blood (i.e H-CN, CO, H-sulfide)
- DNA strand breaks (polycyclic aromatic hydrocarbons, PAH)
- allergic responses via isocyanates
15
Q
List 5 groups of disease states caused by air pollutants
A
- Rhinitis and laryngitis
- tracheitis, bronchitis, bronchiolitis
- asthma and COPD
- cancer
- interstitial disease
16
Q
What causes rhinitis and laryngitis?
A
large particles are deposited in the nose, pharynx and larynx
more soluble gasses are absorbed by the URT mucous membranes causing edema and mucous hypersecretion
17
Q
what causes tracheitis, bronchitis and bronchiolitis
A
large particles are deposited and then cleared by the cilia
small particles and fine fibers are deposited in bronchioles and bifurcations of alveolar ducts
less soluble gasses penetrate to deeper small airways
18
Q
how do air pollutants cause asthma and COPD
A
allergens and irritants are deposited in large airways by turbulent flow, causing chronic inflammatory changes
19
Q
how do air pollutants cause cancer
A
carcinogens (asbestos, polycyclic aromatic hydrocarbons) come into contact with bronchial epithelia cells, causing mutations in proto-oncogenes and tumor-suppressor genes
more than one such contact results in malignant transformation
20
Q
how do air pollutants cause interstitial disease
A
small particles and fibers are deposited in terminal bronchioles, alveolar ducts and alveoli
penetration to the interstitium results in fibrosis and the formation of granulomas
21
Q
How do you minimize/prevent air pollutant exposure
A
- industrial hygiene
- engineering–> replacing or redesigning unsafe equipment or processes
- administrative controls–> retraining, surveillance
- work practice controls–>locks, ventilation
- PPE–>masks, barriers - public health and government
- sentinel cases
- surveillance of known diseases
- regulations (occupational and environmental)
- universal vs. protection of vulnerable populations - individual awareness and prevention
22
Q
list two reactive oxygen species
A
H2O2, NOx
23
Q
list a strong acid that may be found as an air pollutant
A
sulphuric acid
24
Q
what air pollutants may displace oxygen by a simple gradient
A
CO2, methane, N2
25
what air pollutants may disrupt O2 carrying capacity
H-CN, CO, H-S
26
what air pollutants may break DNA strands
polycyclic aromatics, PAH
27
what air pollutant may cause allergic responses
isocyanates
28
describe normal pleural fluid
- about 8 mL per side
- normally at a steady state-->absorption = production
- not visible on CXR or CT scan
- pH normally = 7.6
29
how much pleural fluid is required to be able to visualize a pleural effusion on CXR?
150 mL
30
what blood vessels supply the pleural surfaces?
systemic blood vessels--NOT from pulmonary circulation
31
what is the driving forces behind pleural fluid formation?
formation is as a result of differences in hydrostatic and osmotic pressure between vessels and the pleural space
described by STARLINGS EQUATION
fluid is continually produced by the parietal pleura and enters the pleural space due to an imbalance in hydrostatic and oncotic pressures
32
which pleura is felt to be more important surface for fluid formation?
parietal pleura
33
how is fluid reabsorbed in the parietal pleura
due to lymphatic drainage
34
what is hydrostatic pressure
pressure exerted by the liquid at equilibrium
*pushes fluid out of capillaries
35
what does the hydrostatic pressure in the lungs reflect?
Pulmonary venous pressure
36
what is oncotic pressure
pressure generated by proteins and osmoles in the plasma
draws fluid into capillaries
37
state starlings equation and name its components
Qf = Kf X A [(Pc - Pis) - ơ((πc – πis)]
```
Qf = net flow of fluid
Kf = capillary filtration coefficient/ permeability coefficient
A = surface area of membrane
P = hydrostatic pressure
ơ = reflection coefficient (0-1)
π = colloid osmotic (oncotic) pressure
```
```
c = capillary
is = interstitial
```
38
what is the hydrostatic pressure of the parietal pleura
+ 30 cm H2O
| pushes fluid into pleural space
39
what is the hydrostatic pressure of the pleural space
-5 cm H2O
| pulls fluid into pleural space
40
what is the hydrostatic pressure of the visceral pleura
+ 24 cm H2O
| pushes fluid into pleural space
41
what is the oncotic pressure of the parietal pleura
+34 cm H2O
| pulls fluid into parietal pleura
42
what is the oncotic pressure of the visceral pleura
+34 cm H2O
| pulls fluid into the visceral pleura
43
what is the oncotic pressue of the pleural space?
+ 5 cm H2O
| pulls fluid into the pleural space
44
what is the net pressure gradient (hydrostatic and oncotic) between the pleural space and the visceral pleura?
no net gradient
| 24 + 10 pulls into pleural space, and 34 pulls out into visceral pleura
45
what is the net pressure gradient (hydrostatic and oncotic) between the pleural space and the parietal pleura?
+ 6
| 30 + 10 pushing/pulling into pleural space, and 34 pulling out into parietal pleura
46
list factors that may cause increased fluid entry into pleural space
1. increased permeability (exudate)--K constant--i.e disruption to endothelial layer
2. increased microvascular pressure--i.e in CHF
3. decreased pleural pressure--i.e in atelectasis
4. decreased plasma oncotic pressure--i.e in nephrotic syndrome, hypoalbuminemia
5. infection, malignancy or inflammation
47
list factors that may cause decreased fluid exit
1. factors that impair lymphatic drainage may lead to decreased absorption of pleural fluid by the parietal pleura
2. accumulation of fluid is likely multifactorial in many disease states
48
hepatic hydrothorax
transudative pleural effusion, usually greater than 500mL in patients with portal HTN without any other underlying primary cardiopulmonary cause
most likely develops because of diaphragmatic defects that allow for passage of fluid from the peritoneal space to the pleural space
sucked into chest across diaphragm from abdomen
49
urinothorax
transudative pleural effusion
urine in the pleural space secondary to obstructive uropathy
urine arrives in the pleural cavity either retroperitoneally under the posterior diaphragm or via the retroperitoneal lymphatics
abnormal communication from renal collecting system
50
chylothorax
results from lymph formed in the digestive system accumulating in the pleural cavity due to either disruption or obstruction of the thoracic duct
turbid, milky white appearance
abnormal communication from thoracic duct
51
what is transudate
- LOW protein and lactate dehydrogenase (LDH) in pleural fluid
- implies INTACT endothelial membrane
- fluid accumulation from INCREASED HYDROSTATIC pressure or DECREASED ONCOTIC pressure
clear
52
what is exudate
- HIGH protein and lactate dehydrogenase (LDH) in pleural fluid
- implies DISRUPTION of endothelial membrane
cloudy
53
what is Light's criteria?
85% sensitive for exudate if one of the following; 96% sensitive if 3 of the following
1. fluid protein/serum protein > 0.5
2. fluid LDH/serum LDH >0.6
3. fluid LDH > 2.3 upper limit of normal
54
differential diagnosis of transudate
LUCKI ME
```
Liver (hepatic hydrothorax)
Urinothorax
CHF
Kidney (low protein state--nephrotic)
Iatrogenic
Myxedema (severe hypothyroidism)
Embolic (small %)
```
55
DDx for exudate
everything else
```
includes
malignancy
infection
pulmonary embolism
serositis due to connective tissue disease etc...
```
56
list 3 days lung cancer can cause a pleural effusion
1. increase in permeability
2. physical obstruction of pleural lymphatic vessels (preventing drainage of pleural fluid)
3. indirect ("paramalignant")
57
how does lung cancer cause an increase in permeability leading to pleural effusion
- causes breakdown of epithelium of the blood vessels that supply the pleural surfaces, allowing fluid to leak out into the pleural space
- other things that can also cause disruption to the endothelial layer: infection, inflammation
58
how does lung cancer cause a "paramalignant" state leading to pleural effusion?
1. hypoproteinemia (lower oncotic pressures)
2. postobstructive pneumonitis
3. treatment related (esp radiation)
4. Pulmonary embolism
5. mediastinal node involvement
6. bronchial obstruction
7. pericardial involvement
8. thoracic duct obstruction
59
primary lung cancer leading to pleural effusion
mesothelioma (secondary to asbestos exposure)
60
metastatic cancer leading to pleural effusion
much more common
```
lung
breast
lymphoma
GI/GU
ovarian
```
61
what are the two ways cancers can spread to the pleural space
1. pleural spread of primary lung tumor (dissemination)
| 2. hematogenous spread of the extra-pulmonary malignancy
62
how does nicotine enter the body
inhaled and rapidly absorbed from alveoli (reaches brain in approx. 10 seconds)
absorbed from skin and mucous membranes
63
half life of nicotine
1-2 hours
64
what compound metabolizes nicotine
CYP2A4
65
What is the major metabolite of nicotine and how is this used
major metabolite = COTININE (inactive)
used as a marker for nicotine use (because half life is about 15 hours)
66
how does nicotine act on the body's receptors? what neurotransmitters are released as a result of nicotine use?
- nicotine receptor agonist Alpha4Beta2 causes increased DOPAMINE release which stimulates reward pathways in the brain
- also causes release of acetylcholine, norepinephrine, serotonin, beta-endorphin, GABA which affect alertness and mood
- GABA is a major inhibitory neurotransmitter and has a calming effect
67
what is the result of chronic nicotine use on nicotine receptors
receptor upregulation
68
does nicotine increase risk of CV events?
despite the acute effects of nicotine on the CV system, there is no clear evidence that nicotine itself increases risk of CV events
69
what are the effects of nicotine withdrawal?
1. sleep disturbance
2. reduced concentration
3. irritability
4. depression
5. restlessness
6. increased appetite
70
why isnt there a nicotine pill for nicotine replacement therapy
all forms of nicotine replacement therapy bypass the gut because nicotine has a very low bioavailability and is a gastric irritant in high doses
71
list the various forms that nicotine replacement therapy takes
1. gum
2. patch
3. inhaler
4. nasal spray
5. lozenge
6. sublingual tablet
72
how does nicotine replacement gum work?
side effects?
chewed briefly the placed in cheek/buccal mucosa (buccal absorption)
available doses: 2mg and 4mg nicotine (one cigarette has 1-3 mg)
SEs: GI irritation (i.e swallowing gum), local irritation
provides lower peak dose compared to a cigarette but dose is more evenly spread over time
73
how does the nicotine replacement patch work?
side effects?
- transdermal delivery
- provides continuous 24H or 16H release of nicotine
- cannot be titrated accurately (sometimes used as a 'background therapy' and supplemented with gum for acute use because the patch is not a way to selectively control cravings)
SEs: local irritation--best to rotate locations
74
how does the inhaler nicotine replacement therapy work?
- purpose = to replicate the behavior of smoking
- BUT does not replicate the pharmacokinetics: absorption occurs in the oral cavity, not the lungs
SEs: cough, local irritation of the mouth and throat
75
how does the nasal spray nicotine replacement therapy work?
SEs?
-faster absorption--somewhat mirrors pharmacokinetics of a cigarette
SEs: local irritation of the nose and throat
76
List drugs used as smoking cessation therapies
1. Varenicline (Champix)
2. Bupropion (Zyban)
3. Nortriptyline
77
mechanism of action of full nicotinic agonists/ "nicotine replacement therapy"
full agonist of the nicotine receptor
tries to replace nicotine without replicating the rapid onset and offset of nicotine inhaled through the cigarette smoke
78
name a partial nicotinic agonist
Varenicline (Champix)
79
MOA of varenicline
- partial agonist at nicotine (Alpha4Beta2) receptors
- by binding partially it provides a low level stimulation of nicotine receptors and low level release of dopamine when nicotine is not present
- also prevents binding when patient is smoking---> BLUNTS REWARD of smoking
- likely has BETTER EFFICACY than bupropion and NRT
80
SEs of varenicline
```
depression
agitation
hostility
behavioural changes
suicidality
small increase in risk of CV disease
```
81
Name a noradrenaline and dopamine reuptake inhibitor (NRDI)
Bupropion (Zyban)
82
what is another name for Bupropion? what is it used for?
Wellbutrin--same thing as Bupropion but marketed for depression
drug was first developed as an antidepressant
83
MOA of bupropion
reuptake inhibitor--inhibits reuptake of dopamine and noradrenaline so they have a higher concentration in the synaptic cleft
may also act as a nicotinic receptor antagonist (would blunt smoking reward)
has similar efficacy to NRT
84
SEs of bupropion
insomnia
dry mouth
nausea
SEIZURES (contraindicated in seizure disorders)
safety issues (impulsivity, suicidality)
behavior issues with youth--general concern with all antidepressants
85
why would you not prescribe bupropion with an MAO inhibitor?
MAO inhibitors inhibit the breakdown of neurotransmitters like dopamine and norepinephrine--if prescribed together, these drugs may lead to complications such as a hypertensive crisis
86
MOA of noritriptyline
inhibits reuptake of serotonin and noradrenaline
minimal effects on dopamine uptake
also an antidepressant
not approved in canada
87
SEs of noritriptyline
anticholinergic side effects
88
what is the diagnostic pathway of imaging for lung cancer detection
1. CXR and CT-->discovery of a lung nodule or mass
2. CT--> characterization of the abnormal tissue
3. CT, MRI and PET--> determine if mass can be surgically removed by searching for enlarged, metabolically active lymph nodes and invasion into adjacent tissue
search for distant metastatic lesions
89
Lung cancer: what is visible on a CXR
vessels, pleura and mediastinal structures (outlined by air)
lung cancer creates abnormal soft tissue that displaces air--visible region of abnormal density
90
lung cancer: do you take the CXR on inspiration or expiration?
inspiration
exception is in pneumothorax
91
limitations of CXR in lung cancer evaluation
because it is a projection image, you can't reliable characterize density, ID enlarged lymph, detect chest wall/mediastinal/cardiac invasion, or detect metastatic disease
92
why would you use IV contrast with a CXR?
the contrast increases the density of flowing blood
allows separation of lung lesions with small blood vessels (inflammation/cancer) from avascular lesions which represent fibrosis
fibrotic lesions will not enhance, unlike the highly vascularized masses
most definitive way to diagnose benign versus malignant growth is to compare with previous films
93
what are the benefits of using a CT in lung cancer imaging
- provides 1000 views around the patient, providing cross sectional imaging for better characterization of masses
- CT scans are used to determine if mass is benign versus malignant and for cancer staging
94
characteristics of a "definitely benign mass" on CT
1. unchanging in size for over 5 years
2. less than 2 cm in diameter, completely calcified--granuloma
3. less than 2 cm in diameter with focal areas of fat inside the mass--hematoma
95
characteristics of a "probably benign" mass on CT
1. less than 2 cm in diameter, smooth margins, solitary nodule--previous granulomatous disease
2. less than 2 cm in diameter with satellite nodules--previous or active infection
96
characteristics of a "probably malignant" mass on CT
1. greater than 2 cm in diameter
2. speculated margins
3. bubble or central lucencies (air filled airways running through the lesion)
97
why would you use an MRI to image lung cancer
-enhanced contrast sensitivity over CT--> good for soft tissue scans, especially the brain; good to determine the degree of soft tissue (chest wall) invasion, thereby helping determine if the mass is resectable or not
98
drawbacks to MRI in lung cancer imaging
1. limited signal to noise ration
2. minimal signal from normal lung
*MRI is no better than CT for nodal metastatic disease--> use PET
99
why would you use a PET scan in lung cancer imaging
- uses fluorodeoxyglucose to measure metabolic activity and is a marker of malignant biological behaviors
* active inflammation can be falsely positive
* low grade tumors can be falsely negative
-ability to fuse CT images for PET/CT scans
100
can PET be used to image the brain?
no--tracer does not cross BBB
101
which imaging modality is best to determine distal metastases from lung cancer?
whole body PET (superior to whole body CT) to determine distal metastases, except for brain
102
what are the contrast mechanisms of MRI
- T1/T2 relaxation time
- proton density
- flow
103
what imaging technique do you use to diagnose nodal involvement in lung cancer
PET scan
104
what is a pulmonary nodule
A pulmonary nodule is a small round or oval-shaped growth in the lung. It is sometimes also called a spot on the lung or a coin lesion. Pulmonary nodules are generally smaller than 3 centimeters in diameter. If the growth is larger than that, it is known as a pulmonary mass.
105
what is the risk for malignancy associated with a pulmonary nodule
10% (some notes say up to 68% but 10% is the lower end)
106
what is the etiology of most benign nodules?
infectious granulomas--benign neoplasms such as hamartomas account for
107
what is the goal of evaluation of a nodule
to determine the probability of malignancy in any nodule to justify resection or biopsy versus observation
108
DDx of pulmonary nodule
1. metastatic cancer
2. lung abscess
3. sarcoidosis
4. arteriovenous malformations
5. methotrexate-induced
6. paragonimiasis
7. bronchogenic carcinoma
8. granulomas (TB, fungal)
9. silicosis
10. rheumatoid nodules
11. eosinophilic granuloma
12. lymphoproliferative cancer
13. coccicioimycosis
14. coal worker's pneumonia
15. hamartomas--benign
16. congenital cysts
17. TB
18. histoplasmosis
19. MAC
20. Wegener's granulomatosis
21. echinococcosis
109
what imaging technique is used to DETECT abnormal lung tissue densities?
initial CXR
calcified or not?
growing? compare with previous films
110
what imaging technique is used for staging/characterization of lung nodules?
CT
- mediastinal invasion (heart, great vessels, trachea, esophagus), contralateral lung mass or nodes, malignant pleural effusion, spinal cord invasion, distant metastatic lesions
- cannot distinguish nodes enlarged from infection versus from metastatic disease
111
what imaging technique is best to assess focal chest wall invasion?
MRI
112
what are CT criteria for chest wall invasion
bone destruction
mass extension into chest wall
pleural thickening
many lung cancers invade chest wall focally and dont cause the above changes
pleural thickening may be reactive and not indicate invasion
113
what stage is classified as unresectable lung cancer
Stage IIIb or higher
-mediastinal invasion (heart, great vessels, trachea, esophagus), contralateral lung mass or nodes, malignant pleural effusion, spinal cord invasion, distant metastatic lesions
114
why do we stage cancers?
prognosis and to assess resectability
115
what is a biomarker
a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological response to a therapeutic intervention
116
what is a prognostic marker
factor that provides information about an outcome regardless of therapy
117
what is a predictive marker
a factor that provides information about the possible effect of therapy (demographics make little difference)
118
what is the cellular progression of cancers (histo)
normal epithelium--> hyperplasia--> squamous metaplasia--> dysplasia--> carcinoma in situ --> invasive carcinoma
119
list some genomic alterations commonly observed in lung cancer
1. EGFR
2. KRAS
3. EML4-ALK translocations
early: 3p21-9p21 Loss of heterozygosity; telomerase dysregulation; --> p15INK4a methylation
intermediate: 8p22-24 loss of heterozygosit, FHIT inactivation (inactivation of a tumor suppressor gene)
late: TP53 inactivation (inactivation of the p53 tumor suppressor gene), and 5p22 loss of heterozygosity
120
describe the EGFR mutations seen in some lung cancers
- somatic "gain of function" mutation in the ATP-binding pocket of tyrosine kinase domain of EGFR
- patients found with mutations clearly respond dramatically to EGFR-TK inhibitors
- found in 10-15% of the population of non-small-cell lung cancer (NSCLC)
- test for activating EGFR mutations if there is sufficient time and tissue (takes 2-3 weeks)
- does not account for all the responses and the stable disease
- T790M and cMET resistance
121
describe the KRAS mutation seen in some lung cancers
found in about 20% of NSCLC
DONT test for it because it doesnt change management (unlike EGFR mutation)
122
describe the EML4-ALK translocations seen in some lung cancers
- formation of fusion gene that drives cancer growth
- negative prognostic variable
- mostly in younger non smokers with adenocarcinoma
- almost mutually exclusive with EGFR mutation
- routinely tested for mutation-- CRIZOTINIB pill significantly changes outcomes
123
what is the current gold standard for lung cancer diagnosis
histology
sometimes this isnt specific enough--some certain cancers cannot be distinguished by simple histology (some adenocarcinomas, squamous cell carcinomas look very similar)
dependent on subjectiveness/pathologist
therefore, we need NOVEL BIOMARKERS to predict disease behavior
124
standard treatment for NSCLC early stage
surgery +/- chemo
125
standard treatment for locally advanced NSCLC
concurrent chemo plus radiation
126
standard treatment for advanced or metastatic NSCLC
palliative chemo and/or radiation
Gefitinib--drug that antagonizes the ATP interaction with the EGFR protein when activated--in cases with overexpression
VEGF inhibitor bevacuzimab
127
therapy for SCLC?
no good targeted therapy available for small cell lung cancer
128
what is the main risk factor for lung and oral cancers
smoking
129
incidence of squamous cell carcinoma (lung)
25%
most commonly found in men and closely correlated with SMOKING history
130
microscopic features of squamous cell carcinoma
1. variably resemble normal squamous epithelium with KERATINIZATION and INTRACELLULAR BRIDGES
2. epithelium adjacent to invasive tumour often shows squamous metaplasia, dysplasia, and carcinoma in situ
3. keratinization may take the form of SQUAMOUS PEARLS or individual cells with dense eosinophilic cytoplasm
4. the features are prominent in highly differentiated tumors and only focally seen in poorly differentiated tumors
5. highly mitotic activity in poorly differentiated tumors
6. squamous metaplasia, epithelial dysplasia, and foci or frank carcinoma in situ may be seen in bronchial epithelium adjacent to the tumor mass
131
macroscopic features of squamous cell carcinoma
1. in the past most were seen to arise CENTRALLY from the segmental or subsegmental bronchi, however the incidence on the peripheral lung is increasing
2. often CAVITATE
132
name the 4 major types of lung cancer
1. adenocarcinoma
2. small cell carcinoma
3. large cell carcinoma
4. squamous cell carcinoma
+mesothelioma
133
incidence of adenocarcinoma (lung)
50%
most common type of lung cancer in women and in non smokers
incidence has increased significantly in the last two decades
BAC = bronchoalveolar adenocarcinoma in situ
134
what is the most common type of lung cancer in women and in non smokers
adenocarcinoma
135
what are the two subtypes of bronchoalveolar adenocarcinoma (BAC)
1. non-mucinous with columnar peg-shaped or cuboidal cells
2. mucinous, with distinct tall, columnar cells with sytoplasic and intra-alveolar mucin, growing along the alveolar septa
136
microscopic features of adenocarcinoma
1. malignant epithelial tumors with GLANDULAR differentiation of MUCIN PRODUCTION
2. various growth patterns
3. PATTERS: acinar, papillary, bronchoalveolar and solid with mucin formation
4. Bronchoalveolar carcinoma (BAC): varient occurs in the parenchyma in the terminal bronchoalveolar regions (1-9% of all lung cancers)
5. growth of tumor cells along surface of ALVEOLAR WALLS and RESPIRATORY BRONCHIOLES
6. histologically there is no evidence of stromal, vascular or pleural invasion
7. grow along pre-existing structures without destruction of alveolar architecture
137
patters
adenocarcinoma
acinar
papillary
bronchiolalveolar and solid with mucin formation
138
what is BAC
bronchiolalveolar carcinoma
variant occurs in the parenchyma in the terminal bronchiolalveolar regions (1-9% of all lung cancers)
139
macroscopic features of adenocarcinoma (lung)
1. lesions are generally more PERIPHERALLY located compared to squamous cell carcinoma and tend to be SMALLER
2. peripheral tumor associated with PUCKERING of pleura
3. BAC variant always occurs in the PERIPHERAL portions of the lung as a single nodule or more often as diffuse nodules that coalesce to produce PNEUMONIA-LIKE consolidation
4. parenchymal nodules have mucinous gray translusence when secretion is present but otherwise appear as solid--can be confused with pneumonia
140
incidence of small cell carcinoma (lung)
15%
highly malignant, most aggressive of all lung cancers
all are HIGH GRADE
strong association with CIG smoking
widely metastatic
virtually INCURABLE
141
what percent of small cell carcinomas of the lung are incurable at presentation
75%
142
which is the most aggressive of all lung cancers
small cell carcinoma
143
microscopic features of small cell carcinoma
1. small epithelial cells with SCANT cytoplasm, ill defined large borders and finely granular nuclear chromatin (SALT AND PEPPER)
2. absent nucleoli
3. cells are ROUND, OVAL and spindle shaped with nuclear molding
4. generally the cells are smaller than resting lymphocytes
5. high mitotic count--HYPERCHROMATIC nuclei
6. grow in CLUSTERS
7. neither glandular nor squamous
8. basophilic staining of vascular walls is due to encrustation by DNA from nuclear tumour cells
8. NEUROENDOCRINE differentiation
144
macroscopic features of small cell carcinoma
1. occur both in major bronchi and in periphery of lung
| 2. predominantly CENTRAL
145
incidence of large cell carcinoma
10%
146
microscopic features of large cell carcinoma
1. UNDIFFERENTIATED malignant epithelial tumour
2. large POLYGONAL cells with vasicular nuclei, prominent nucleoli, moderate amount of cytoplasm
3. minimal glandular or squamous differentiation is common (probably represent squamous cell carcinomas and adenocarcinomas that are so undifferentiated that no longer can be recognized)
4. NEUROENDOCRINE differentiation (recognized by--organoid nestings, trabecular, rosette-like and palisading patterns)
147
macroscopic features of large cell carcinoma
often peripheral
148
what is the primary neoplasm of the pleura
mesothelioma
149
incidence of mesothelioma
primary neoplasm of the pleura, often associated with asbestos exposure
encases WHOLE lung--directly invades thoracic wall structures
distant mesastases occur late
symptoms include pleural effusion, severe chest pain
poor prognosis (2 years)
150
microscopic features of mesothelioma
3 microscopic patterns:
1. epithelial (better prognosis)
2. sarcomatous
3. mixed
151
macroscopic features of mesothelioma
1. pleural surfaces are seeded with malignant mesothelioma cells forming GROUPED NODULES
2. extensive local spread
3. as disease progresses, covers entire pleural space and invades chest wall, mediastinum and diaphragm
152
why is it important to distinguish between small cell and non-small cell lung cancer?
they are treated differently
NSCLC has better prognosis compared with SCLC
153
best treatment for NSCLC? SCLC?
```
NSCLC = surgery
SCLC = radiation and chemo
```
154
what are the 3 main areas from whence cells are obtained to use for lung cancer diagnosis?
1. lung itself (parenchyma or bronchial tree)
2. mediastinal lymph nodes
3. pleura
155
what are the procedures used to obtain tissue for a histological assessment for lung cancer?
1. bronchial biopsy
2. endobronchial ultrasound (EBUS)
3. mediastinal lymph node biopsy (cancer staging)
4. transbronchial biopsy
5. transthoracic core needle biopsy
6. pleural biopsy
7. open lung biopsy
8. lung resection
156
bronchial biopsy
endoscope inserted into the bronchial tree, locating the cancerous tissue, and finally resecting the tissue
only reserved for cases where cancer has either invaded into the tree or originated from it (central cancers)
not very invasive compared to other techniques
157
EBUS
endobronchial ultrasound
a bronchoscope is inserted through the bronchial tree along with an ultrasound probe, emitting sound waves to evaluate for any abnormalities in the vicinity
if there are, a small amount of tissue is resected and sent for biopsy
158
transthoracic core need biopsy
under guidance of CT, a fine needle is inserted into the best depending on where the cancerous tissue is and tissue is withdrawn
this can be done to collect cancerous tissue from the pleura, lung parenchyma, or the mediastinum
it can also be done under the guidance of fluoroscopy or ultrasound, although CT is preferred
tissue cut and withdrawn
159
pleural biopsy
essentially the same as transthoracic needle biopsy
patient asked to hum while the tube is inserted to prevent pneumothorax
160
open lung biopsy
indicated for withdrawing tissue samples of at least 3cm in diameter
severe cases of lung cancer or multiple primary tumors
much more invasive
161
list the procedures used to obtain tissue samples for cytological assessment of lung cancer
1. sputum coughed up may be used (not invasive, not as useful, only reserved for central cancers)
2. bronchial brushing/washing of tumor during bronchoscopy (only useful for central lesions)
3. EBUS
4. fine needle aspiration (reserved for peripheral cancers or cancers that have spread to the periphery; cells are sucked into a tube and then withdrawn)
5. pleural fluid for ID of malignant cells (only useful when cancer has spread into the pleura, and is actively being shed into the pleural space and fluid as a result of metastatic cancer)
162
what are the key features, essential to diagnosis of mesothelioma
1. unilateral, nonpleuritic chest pain and dyspnea
2. pleural effusion or pleural thickening or both on CXR
3. malignant cells in pleural fluid or tissue
4. distant (>20 years earlier) Hx of exposure to asbestos
163
where do most tumors in mesothelioma arise from?
80% arise from mesothelial surfaces of the pleura
20% arise from peritoneum
164
what percent of pleural mesotheliomas are diffuse?
75% (usually malignant)
165
what is the mean age at onset of symptoms of mesothelioma
60 years
166
what is the usual time between exposure to asbestos and onset of symptoms
20-40 years
167
how are men and women affected by mesothelioma?
men outnumber women 3:1
168
what is the lifetime risk of mesothelioma with asbestos exposure in asbestos workers
10%
169
what is the association between smoking and mesothelioma
smoking significantly increases the risk of bronchogenic carcinoma in asbestos workers and aggravates asbestosis
BUT there is no association between smoking and mesothelioma independent of asbestos
170
what percent of malignant pleural mesothelioma is associated with asbestos exposure
60-80%
171
what are the routes of asbestos exposure
1. mining
2. milling
3. manufacturing
4. shipyard work
5. insulation
6. brake linings
7. building construction and demolition
8. roofing materials
9. other asbestos containing products
172
symptoms and signs of mesothelioma
insidious onset of shortness of breath
nonpleuritic chest pain
weight loss
173
physical findings in mesothelioma
1. dullness to percussion
2. diminished breath sounds
3. finger clubbing in some cases
4. malignant pleural mesothelioma progresses rapidly as the tumor spreads along the pleural surface to involve the pericardium, mediastinum, and contralateral pleura
5. tumor may eventually extend beyond the thorax to involve the abdominal lymph nodes and organs
174
DDx of mesothelioma
1. chronic organized empyema
2. sarcoma
3. metastatic tumor to the pleura, especially adenocarcinoma
4. malignant fibrosing histiocytoma
5. other causes of pleural effusion
175
diagnosis of mesothelioma--lab tests
1. pleural fluid analysis often reveals a hemorrhagic exudate
2. cytologic tests of the pleural fluid are often negative
176
findings on imaging studies of mesothelioma
1. radiographic findings: nodular, irregular, unilateral pleural thickening//varying degrees of unilateral pleural effusion
2. CT helps determine the extent of the pleural involvement
177
mesothelioma diagnostic procedures
1. thoracocentesis
| 2. VATS biopsy is usually necessary to obtain an adequate specimen for histological diagnosis
